แนวทางการรักษาโรคมะเร็งในเด็ก 2557

..
2557
National protocol for the treatment of
childhood cancers 2014
(The Thai Pediatric Oncology Group: ThaiPOG)
(The Thai Society of Hematology)

(.)
(National Health Security Office: NHSO)
.. 2557
National protocol for the treatment of childhood cancers 2014
50 2 10
10310
.. 2557
1,000
. 02-943-8787, 02-508-1114
... .. 2537
:
.. 2557- : : 324
ISBN
978-616-91631-1-4
Thai Pediatric Oncology Group

( )
2557


(Thai Pediatric Oncology group) 15

100
(.)
8

disease management
2
solid tumor
solid tumor
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disease management . 2555

histiocytosis

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. . histiocytois . .
germ cell tumor


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Acute Lymphoblastic Leukemia (ALL)................................................................................................ 1
Management guideline ................................................................................................................... 1
Risk stratification for ALL ............................................................................................................... 1
Risk stratification for infant ALL and relapsed ALL ......................................................................... 2
Time to relapse .............................................................................................................................. 2
Treatment Schema ........................................................................................................................ 3
Dose modification guidelines for chemotherapy toxicity ................................................................. 4
Methotrexate infusion guideline ...................................................................................................... 9
Guide line for dose-modification of oral MTX and 6-MP in maintenance phase ........................... 12
Guidelines for Tyrosine Kinase Inhibitors administration .............................................................. 13
Supportive care guideline ............................................................................................................ 14
Treatment protocol for standard risk acute lymphoblastic leukemia [Thai-POG ALL 1301]........... 16
Treatment protocol for high risk acute lymphoblastic leukemia [Thai-POG ALL 1302] ................. 22
23
30
Treatment protocol for very high risk acute lymphoblastic leukemia [Thai-POG ALL 1303] .......... 29
Treatment protocol for Philadephia chromosome positive acute lymphoblastic leukemia [Thai-POG
ALL 1304] ....................................................................................................................................40
39
Treatment protocol for relapsed acute lymphoblastic leukemia [Thai-POG ALL 1305] ................. 53
Treatment protocol for low risk infant acute lymphoblastic leukemia [Thai-POG ALL 1306] ......... 61
Treatment protocol for intermediate/ high risk infant acute lymphoblastic leukemia [Thai-POG ALL
1307] ........................................................................................................................................... 70
69
Acute Myeloid Leukemia (AML) ........................................................................................................81
82
Risk stratification for AML ............................................................................................................ 82
Treatment schema ....................................................................................................................... 83
Dose modification guidelines for chemotherapy toxicity ............................................................... 84
Supportive care guideline ............................................................................................................ 87
Off therapy follow up guideline..................................................................................................... 88
Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 1301] ........................... 89
Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 1302].......................... 94
Optional treatment protocol for acute myeloid leukemia [Thai-POG AML-02-08] .......................... 99
Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 0106] ............................. 107

Lymphoma .....................................................................................................................................112
Hodgkin disease ........................................................................................................................ 112
Risk stratification ........................................................................................................................ 112
Treatment schema ..................................................................................................................... 115
Dose modification guidelines for chemotherapy toxicity ............................................................. 116
High dose methotrexate infusion guideline ................................................................................. 120
Off therapy follow up guideline................................................................................................... 124
Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] ................................... 125
Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302]............. 131
Data entry form for non-Hodgkin lymphoma............................................................................... 139
Non-Hodgkin lymphoma (NHL) Murphy stage ......................................................................... 140
Treatment plan for patients with NHL......................................................................................... 140
Treatment plan for patiants with mature B-cell lymphoma .......................................................... 141
Treatment plan for patients with anaplastic large cell lymphoma ............................................... 142
Appendix I: Supportive care guidelines for high dose methotrexate administration for ThaiPOGNHL13-BL protocol .................................................................................................................... 143
Appendix II: Supportive care guidelines for high dose methotrexate administration for ThaiPOGNHL13-ALCL protocol ................................................................................................................ 144
Evaluation for matual B cell lymphoma ...................................................................................... 147
Evaluation for Anaplastic Large Cell Lymphoma ........................................................................ 148
Treatment protocol for low risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-LR]
.................................................................................................................................................. 149
Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BLSR] ............................................................................................................................................ 150
Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-HR]
.................................................................................................................................................. 155
Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL-LR]
.................................................................................................................................................. 165
Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL13-ALCL-SR] ............................................................................................................................. 168
Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL-13ALCL-HR] .................................................................................................................................. 171
CNS Germ Cell Tumor ...................................................................................................................174
Data entry form .......................................................................................................................... 174
Treatment protocol for CNS germinoma [ThaiPOG-BT-13-GCT] ................................................ 175
Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT]....................................... 176
Medulloblastoma ........................................................................................................................ 178
Data entry form .......................................................................................................................... 178
Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] ..................... 179

Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR] ............................. 181
Infant Brain Tumors (Age < 3 years old) ........................................................................................183
Data entry form .......................................................................................................................... 183
Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB]............................................... 184
Irradiation guideline.................................................................................................................... 187
High dose methotrexate infusion guideline ................................................................................. 188
Neuroblastoma ...............................................................................................................................190
International neuroblastoma risk group (INRG) staging system .................................................. 190
Pre-treatment risk classification modified by ThaiPOG ............................................................... 191
Schematic treatment .................................................................................................................. 192
Recommended MIBG treatment ................................................................................................. 195
Data entry form .......................................................................................................................... 196
Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR] ....................................... 197
Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR]............................... 198
Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] ..................................... 200
Retinoblastoma ..............................................................................................................................210
Staging system .......................................................................................................................... 210
Pathologic classification (pTNM) ................................................................................................ 211
Investigations ............................................................................................................................. 212
Summary treatment strategy based on laterality and retinoblastoma grouping ........................... 213
Post-treatment evaluation .......................................................................................................... 216
Data entry form .......................................................................................................................... 217
Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01] ...................................................... 218
Treatment protocol for intrathecal in retinoblastoma [ThaiPOG-RB-13-05] ................................. 226
Renal tumor ...................................................................................................................................227
Staging system for renal tumors ................................................................................................ 227
Protocol assignment .................................................................................................................. 228
Radiation therapy dosing guidelines (within 10-14 days after surgery) ....................................... 228
Treatment protocol for Wilms tumor [ThaiPOG-WT-13-01] ........................................................ 229
(Recommended imaging studies for follow-up) ........................................... 244
Hepatoblastoma .............................................................................................................................245
Data entry form for hepatoblastoma ........................................................................................... 245
PRETEXT (Pre-treatment extent of disease) staging system ..................................................... 246

High dose cisplatinum (CDDP) administration protocol .............................................................. 247
Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR] ........................... 249
Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR] ..................................... 251
Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR] ........................ 253
Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR] ................................... 255
Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] ......................... 257
Osteosarcoma ................................................................................................................................260
Data entry form .......................................................................................................................... 260
Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD] ............. 261
Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] ......... 264
Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET] .................................. 268
Ewing Sarcoma Family of Tumors ..................................................................................................272
Data entry form .......................................................................................................................... 272
Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] ................................................. 273
Follow up schedule after complete treatment ............................................................................. 276
Anthracycline record sheet......................................................................................................... 277
Guideline for administration of high dose cyclophosphamide/ ifosfamide ................................... 278
Rhabdomyosarcoma.......................................................................................................................279
Data entry form .......................................................................................................................... 279
Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1] ......................................... 282
Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2] ......................................... 284
Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-SR] .......................................... 287
Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-HR] .......................................... 290
Germ Cell Tumor............................................................................................................................293
Staging of germ cell tumor (gonadal and extragonadal) ............................................................. 293
gonadal and extragonadal germ cell tumor ......................................... 294
Type of germ cell tumor by staging and by risk group ............................................................... 295
germ cell tumor histology staging ........................ 295
PEB JEB .......................................................................................... 295
Data entry form .......................................................................................................................... 296
Treatment protocol for germ cell tumor [ThaiPOG-GCT-13] ....................................................... 297
cisplatinum (CDDP) ......................................................................................................... 298
.................... 298
Histiocytosis ...................................................................................................................................299
Langerhans cell histiocytosis...................................................................................................... 299
Disease stratification .................................................................................................................. 299
Definition of organ involvement .................................................................................................. 299

LCH treatment guideline ............................................................................................................ 300
Data entry form .......................................................................................................................... 301
Treatment protocol for Langerhan cell histiocytosis.................................................................... 303
Hemophagocytic lymphohistiocytosis ......................................................................................... 307
Data entry form .......................................................................................................................... 307
Treatment protocol for hemophagocytic lymphohistiocytosis ...................................................... 309
Acute Lymphoblastic Leukemia (ALL)

Management guideline
Risk stratification for ALL
Standard Risk (SR)
Clinical criteria
Pre-B ALL
o Age 1-9 and
o WBC < 50,000
Molecular criteria (optional)
Day 29 BM MRD < 0.01%
No unfavorable molecular
feature
High Risk (HR)

Very High Risk (VHR)
Clinical criteria
Clinical criteria
T-ALL
Pre-B ALL
o Age >= 14
Pre-B ALL
o Age 10-13 or
CNS-3
o WBC >= 50,000
Induction failure (M2 or M3 at
Testicular disease
day 29)
Steroid pretreatment
Day 29 BM MRD >= 0.01
with no favorable cytogenetic
Day 29 BM MRD >= 0.01%
with favorable cytogenetic:
Unfavorable
molecular
ETV-6/RUNX-1 or double
feature
trisomy 4,10
o iAMP 21
o MLL arrangement
o Hypodipliody (< 44
chromsome or DNA
index < 0.81)
o Ph-chromsome (follow
Ph-ALL protocol)
Definition:
Initial WBC: The first WBC at the treating institution, or the WBC prior to intravenous fluids,
whichever occurred first.
MRD: Minimal residula disease
Steroid pretreatment:
o If steroids are given for more than 24 hours in the 2 weeks prior to diagnosis, the patient will
be assigned to receive induction therapy on the HR protocol
o Any amount of steroid pretreatment at any time prior to 2 weeks before diagnosis will not
affect initial induction assignment.
o Inhalational steroids are not considered as pretreatment.
CNS leukemia at diagnosis:
o CNS 1: CSF, absence of blasts on cytospin, regardless of the number of WBCs
o CNS-2:
CSF, < 5/ul WBCs and cytospin positive for blast.
Acute Lymphoblastic Leukemia (ALL): Management guideline

Traumatic LP with cytospin positive for blasts but negative Steinherz/Bleyer
algorithm.
o CNS-3:
CSF, >= 5/ul WBCs and cytospin positive for blast.
Traumatic LP with cytospin positive for blasts and positive Steinherz/Bleyer
algorithm.
Clinical signs of CNS leukemia such as facial nerve palsy, brain/eye involvement or
hypothalamic syndrome.
o Steinherz/Bleyer algorithm for traumatic lumbar puncture:
Positive if CSF WBC/CSF RBC > 2 X Blood WBC/ Blood RBC
Testicular leukemia at diagnosis: unilateral or bilateral testiculomegaly. Biopsy is required if clinical
finding are equivocal or suggestive of hydrocele or non-leukemia mass.
Bone marrow status:
o M1: < 5% lymphoblasts
o M2: 5-25% lymphoblasts
o M3: > 25% lymphoblasts
Risk stratification for infant ALL and relapsed ALL
Infant ALL
Low Risk
Age < 1 y/o at diagnosis and
No MLL rearrangement
Relapsed ALL
Immunophenotype
Non T-cell
T-cell
Intermediate Risk
Age >= 90 days to < 1 y/o at
diagnosis with MLL
rearrangement
High Risk
Age < 90 days at diagnosis with
MLL rearrangement
Site of relapse
Very early
Early
Late
Isolated extramedullary
High
Intermediate
Standard
Isolated marrow
High
High
Intermediate
Combined
High
Intermediate
Intermediate
Isolated extramedullary
High
Intermediate
Standard
Isolated marrow
High
High
High
Combined
High
High
High
Time to relapse
1. Very early: less than 18 months from first diagnosis
2. Early: 18 months or more after first diagnosis and less than 6 months from stopping therapy
3. Late: 6 months or more after stopping therapy
Acute Lymphoblastic Leukemia (ALL): Risk stratification for infant ALL and relapsed ALL

Treatment Schema
Protocol assignment and treatment schema for new ALL patient
Acute Lymphoblastic Leukemia (ALL)
Standard Risk (SR)

Induction (3 drugs)
Very High Risk (VHR)
High Risk (HR)
Infant ALL
See Infant
protocol
Induction (4 drugs)
Ph + ALL
Follow Ph+ ALL protocol
+ HR /VHR feature
- HR /VHR feature
Consolidation
Augmented Consolidation
IM-I
Augmented IM-I
DI
Augmented DI
Induction failure and

hypodiploidy
Proceed to BMT
with best available
donor
VHR
Maintenance
HR
IM-II
Maintenance
Note:
IM = Interim maintenance, DI = Delayed intensification
Patient with testicular disease at diagnosis with persistent disease by the end of induction will
receive testicular XRT during consolidation
CNS-3 patient will receive cranial irradiation during maintenance cycle 1
Infant ALL: ALL patient with age < 1 y/o will use infant ALL protocol
Ph+ ALL: BCR-ABL fusion transcription determined by FISH or RT-PCR or t(9,22)(q34;q11)
determined by cytogenetic. ALL patients with BCR-ABL translocation will move to Ph+ ALL
protocol on day#15 of induction or as soon as BCR-ABL feature is reported.
Acute Lymphoblastic Leukemia (ALL): Treatment Schema

Treatment schema: Philadelphia-positive ALL
Treatment schema: Infant ALL

INF-Induction
SR-Induction drugs)
HR/VHR-Induction
BCR-ABL +
INF-Induction-Intensification
PH-Induction
INF-Re-Induction
PH-Consolidation-I
PH-Consolidation-II
INF-Consolidation
PH-IM-I
Donor -
Donor +
PH-DI-I
LR-INF-Continuation-I
HR-INF-Continuation-I
HR-INF-Continuation-II
HR-INF-Continuation-III
HR-INF-Continuation-IV
HSCT
PH-DI-I
LR-INF-Continuation-II
HR-INF-Continuation-V
PH-IM-II
INF-Maintenance
PH-Maintenance
INF-Maintenance
Schema for treatment of relapsed ALL (ThaiPOG-ALL-13-REL)

Standard
Intermediate
Phase 1
Phase 1
MRD
NEG
High
Phase 1
POS
Phase 2
Phase 2
Phase 3
Phase 3
Localized
radiotherapy
MRD
POS
Phase 5
Phase 4
NEG
Allo SCT
Phase 6
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity

Dose modification guidelines for chemotherapy toxicity
Asparaginase
o Allergy:
Local allergic reactions (inflammation at injection site, swelling, transient flushing or rash, drug
fever < 38 C): continue asparaginase administration.
Systemic allergic reactions: discontinue asparaginase administration.
Anaphylaxis (symptomatic bronchospasm with or without urticaria, allergy related angioedema,
hypotension, parenteral intervention indicated): discontinue future asparaginase therapy.
Suplement L-ASP with Erwinia ASP or escalate treatment to higher risk regimen without
asparaginase and consider HSCT with matched sibling.
o Coagulopathy: If symptomatic, hold asparaginase until symptoms resolve, then resume with the next
scheduled dose. Consider factor replacement. Do not withhold dose for abnormal lab finding without
clinical symptoms.
o Hyperbillirubinemia: Consider withhold dose in patient with an elevated direct billirubunemia. (no specific
guideline available)
o Hyperglycemia: Do not modify dose. Treat hyperglycemia as medically indicated.
o Ketoacidosis: Hold asparaginase until blood glucose can be regulated by insulin.
o Hyperlipidemia: Do not modify dose.
o Pancreatitis:
Mild pancreatitis: Held dose until symptoms and signs subside and amylase level return to
normal then resumed.
Severe or hemorrhagic pancreatitis: Discontinue future asparaginase therapy.
o Thrombosis: Withhold asparaginase until treat with appropriate antithrombotic therapy. Upon resolution of
symptoms consider resume asparaginase while continuing LMWH or antithrombotic therapy. Do not
withhold dose for abnormal lab finding.
o CNS event (bleed, thrombosis or infarction): Withhold asparaginase until treat with appropriate therapy.
Resume full dose when all symptoms have resolved.
Cyclophosphamide/Ifosphamide
o Hematuria: Omit in the presence of macroscopic hematuria. If there is a history of significant hematuria,
hydrate before cyclophosphamide until urine specific gravity is < 1.010 and hydrate at 125 ml/m2/h for 24
hours after dose. Monitor for adequate urine output. Give IV MESNA at 60% dose of cyclophosphamide
dose divided to 3 doses. Give first dose MESNA 15 minutes before chemo dose and repeat 4 and 8
hours after the start chemo.
o Renal dysfunction: if GFR < 10 ml/min/1.73 m2, reduce dose of cyclophosphamide/Ifosphamide by 50%.
Cytarabine
o ARAC Syndrome: Do not withhold ARAC for fever if it is likely to have been caused by the ARAC. Obtain
blood cultures. For rash or conjunctivitis, withhold for grade 3-4 toxicity until resolved. Make up missed
doses and consider concurrent treatment with hydrocortisone or dexamethasone, and/or with

dexamethasone ophthalmic drops for conjunctivitis. Once Consolidation (C) or Delayed Intensification (DI)
has started do not interrupt for uncomplicated myelosuppression; do hold for proven or presumed serious
infection. Do make up missed doses.
Doxorubicin
o Cardiac toxicity: Discontinue for clinical or echocardiographic evidence of cardiomyopathy (SF < 27% of
EF < 50%)
o Myelosupression (beyond induction): Delay anthracycline if patient has severe infection or grade 3-4
mucositis and NAC < 500/uL during phase other than induction.
o Extravasation: Discontinue IV administration of the drug. Apply cold compression for 20 minutes at least 4
times a day.
o Hyperbillirubinemia:
Direct Bili (mg/dL) % Dose reduction
< 1.2
Full dose
1.2-3.0
50%
3.1-5.0
75%
>5.0
Withhold dose nad administer next scheduled dose if toxicity has resolved. Do not
make up missed doses.
Etoposide
o Allergic reaction: Premedication with diphenhydramine 1-2 mg/kg slow IV push, max dose 50 mg. If
symptoms persist, add hydrocortisone 100-300 mg/m2.
o Hypotension: If SBP or DBP fall 20 mm Hg during infusion, reduce infusion rate by 50%. Start
simultaneous infusion of NDS 10 ml/kg if BP fail to recover or fall further. Stop infusion if BP does not
recover and conitne NS. Prehydrate with 0.9% NS at 10 ml/kg/h for 2 hours if patient have prior episode
of hypotension.
o Renal insufficiency: If CrCL 10-50 ml/min/1.73m2, decrease dose by 25%. If CrCl < 10 ml/min/1.73 m 2,
decrease dose by 50%.
o Hyperbillirubinemia: Direct billirubinemia > 2 mg/dl, decrease dose by 50%. Direct bilirubinemia > 5 mg/dl,
hold etoposide.
IT-Methotreaxate
o Systemic toxicity: Do not reduce the dose of IT-MTX for systemic toxicity (myelosupression, mucositis,
etc.). Instead, leucovorin may be used at a dose of 5 mg/m2/dose every 12 hours x 2 doses, beginning 48
hours after the IT-therapy.
IV-Methotrexate
o Please see MTX infusion guideline.
PO Methotrexate and 6-Mercaptopurine
o Interim Maintenance-I with HD MTX for HR/VHR

Hold 6-MP if ANC < 750/uL and/or platelets < 75,000/uL. Restart 6-MP at full dose with next HD
MTX when ANC is > 750/uL and platelets >= 75,000/uL. Do not make up missed dose. Consider
a marrow evaluation for persistent cytopenias.
o Maintenance:
See PO-MTX and 6-MP dose modification guideline in maintenance.
Steroids (Dexamethasone and Prednisone)
o Hypertension: Doses should not be reduced. Sodium restriction and anti-hypertensive should be
employed. Avoid calcium channel blockers due to prohemorrhagic effect.
o Hyperglycemia: Dose should not be reduced for hyperglycemia. Insulin therapy should be employed to
control blood sugar.
o Pancreatitis: Discontinue steroid in a presence of severe or hemorrhagic pancreatitis.
o Osteonecrosis: Do not modify steroid therapy during induction or delayed intensification. Omit
Maintenance steroid for OS grade 2 or greater. Consider resuming maintenance steroid after 6 months if
joint symptoms resolved or MRI show significant improvement.
o Varicella: Steriod should be held during active infection except during induction.
o Inability to use oral doses:
Dexamethasone: substitute the IV preparation mg for mg
Prednisone: Substitue IV methylprednisone at 80% of oral prednisone dose.
Severe infection: Do not hold or discontinue steroid during induction. Later in therapy, one may
consider holding steroid until patient cardiovascular stability. Except stress doses.
Sever psychosis: Dexamethasone dose may reduce by 50% for severe psychosis. If symptoms
persist, switch to prednisone.
PO 6-Thioguanine (6-TG)
o Delayed intensification: Oral 6-TG should be held for suspected or serious infection.
o Liver dysfunction: For clinical jaundice, hepatomegaly or splenomegaly during or within 2 weeks of
completing the 2 week course(s) of thioguanine, obtain an ALT/AST/total and direct bilirubin. Consider
Doppler ultrasound with an assessment for ascites and portal blood flow to assess for possible sinusoidal
obstruction syndrome (SOS; formerly veno-occlusive disease, VOD). Hold thioguanine for a direct bilirubin
of > 2.0 mg/dL or for new onset hepatomegaly or splenomegaly until SOS is ruled out. SOS may also
present with unexplained thrombocytopenia and splenomegaly. Consider Doppler ultrasound in the
presence of these symptoms. No further thioguanine should be administered in a patient with SOS.
Vincristine
o Severe neuropathic pain (grade 3 or greater): Hold dose(s). When the symptoms subside, resume 50%
previous calculated dose (Max: 1 mg) then escalate to full dose as tolerated. Severe peripheral
neuropathies might suggest the nedd for evaluation to rule out Charcot Marie Tooth Disease.
o Vocal cord paralysis: Hold dose(s). When the symptoms subside, resume 50% previous calculated dose
(Max: 1 mg) then escalate to full dose as tolerated. Consider work up for Charcot Marie Tooth Disease.

o Foot Drop, paresis: These toxicities are largely reversible over months to years. Consider hold or
decrease dose of VCR but it wont result in rapid resolution of symptoms. Consider physical therapy
evaluation.
o Jaw pain: Treat with analgesics; do not modify vincristine dose.
o Hyperbillirubinemia:
Direct Bili (mg/dL) % Dose reduction
< 3.1
Full dose (maximum dose: 2 mg)
3.1-5.0
50% (maximum dose: 1 mg)
5.1-6.0
75% (maximum dose: 0.5 mg)
>6.0
Withhold dose and administer next scheduled dose if toxicity has resolved. Do not
make up missed doses.
o Constipation or ileus (>= grade 3) or typhilitis: Hold dose(s). Institute aggressive regimen to treat
constipation. When the symptoms subside, resume 50% previous calculated dose (Max: 1 mg) then
escalate to full dose as tolerated.
o Extravasation: Discontinue IV administration of the drug. Apply warm compression for 20 minutes at least
4 times a day for 1-2 days. Consider surgical consultation.
Modified (Balis) Pediatric Scale of Peripheral Neuropathies
Peripheral Motor Neuropathy:
Grade 1 Subjective weakness, but no deficits detected on neurological exam, other than abnormal deep
tendon reflexes.
Grade 2 Weakness that alters fine motor skills (buttoning shirt, coloring, writing or drawing, using eating
utensils) or gait without abrogating ability to perform these tasks.
Grade 3 Unable to perform fine motor tasks (buttoning shirt, coloring, writing or drawing, using eating
utensils) or unable to ambulate without assistance.
Grade 4 Paralysis.
Peripheral Sensory Neuropathy:
Grade 1 Paresthesias, pain, or numbness that do not require treatment or interfere with extremity function.
Grade 2 Paresthesias, pain, or numbness that are controlled by non-narcotic medications (without causing
loss of function), or alteration of fine motor skills (buttoning shirt, writing or drawing, using eating utensils) or
gait, without abrogating ability to perform these tasks.
Grade 3 Paresthesias or pain that are controlled by narcotics, or interfere with extremity function (gait, fine
motor skills as outlined above), or quality of life (loss of sleep, ability to perform normal activities severely
impaired).
Grade 4 Complete loss of sensation, or pain that is not controlled by narcotics.

Methotrexate infusion guideline
Hold bactrim, NSAID, penicillins, PPI or aspirin containing medication on the day of IV MTX infusion and
for at least 72 hours after start MTX infusion.
Dose modification:
o Nephrotoxicity: Postpone course if serum Creatinine > 1.5 x baseline or GFR < 65 ml/minute/1.73m 2. If
renal function does not recovery, omit MTX.
o Liver dysfunction:
ALT
IV MTX
< 10 X ULN
Continue therapy as scheduled.
10 -20 X ULN
Continue therapy as scheduled for 1 cycle
10 -20 X ULN for 2 consecutive cycle Discontinue Bactrim switch to other PCP prophylaxis. Hold therapy
until ALT < 10 X ULN then resume full dose. Do not skip dose.
>20 X ULN
Hold therapy until ALT < 10 X ULN then resume full dose. Do not
skip dose.
>20 X ULN for > 2 weeks
Evaulate AST, Billi, ALK, PT, Albumin, TP, Hepatitis A, B, C, CMV
and EBV serology. Consider liver biopsy before additional therapy
given.
Hold IV MTX for direct hyperbillirubinemia > 2.0 mg/dl
o Mucositis: Hold IV MTX for grade 3-4 mucositis until resolved. Increase leucovorin rescue following the
next course to 5 doses on a Q 6 H schedule. If mucositis recurs despite the extended leucovorin,
decrease the dose of MTX by 25% and increase hydration to 200 ml/m 2/h with 5 doses of leucovorin.
Should subsequent courses be well tolerated, use a stepwise approach to resuming full MTX dose.
o Myelosupression: All chemotherapy should be held for ANC < 750/ul and platelet < 75,000/ul
HD-MTX infusion:
o Prehydration: D5 NS + 30 mEq NaHCO3/L at 125 ml/m2/h until urine spec <= 1.010 and pH is between
7-8. Adjust fluid volume or sodium bicarbonate to maintain urine spec and pH above. Bicarbonate bolus
(25 mEq/m2 in 15 min) can be given to raise urine pH quickly. Continue hydration and alkalinization for
minimum of 48 hours after complete infusion.
o Infusion: 10% of total MTX dose in 65 ml/m2 D5 1/4NS with 30 mEq NaHCO3/L infuse over 30 min. Then
follow immediately with 90% of total MTX dose in 2,935 ml/m2 D5 NS with 30 mEq NaHCO3/L over
23.5 hours at rate 125 ml/m2/h. MTX infusion should complete in 24 hours. 26 hours infusion is
acceptable but not encouraged.
Acute Lymphoblastic Leukemia (ALL): Methotrexate infusion guideline

Monitor MTX level and Cr at 24 and 48 hours after start MTX infusion
MTX toxicity- recommendation for management
o For elevated MTX level or delayed excretion monitor serum creatinine q 12-24 hours and MTX level q 24
hours.
o Doses of leucovorin > 25 mg PO should be given IV due to saturation of absorption. Leucovorin contain
calcium and should not be given at the rate faster than 160 mg per minute.
o During MTX administration maintain urine pH 7-8 at all times.
o Mucositis grading system
Severity
Stomatitis
Gastritis
Colitis
Grade I
Painless ulcers, erythema or mild soreness in the absence
of lesion
Grade II Painful erythema, edema or Requiring
medical Abdominal pain with mucus
ulcers but can eat or swallow management or non-surgical and/or blood in stool
treatment
Grade III Painful erythema, edema or Bleeding without perforation, Abdominal pain, fever,
ulcers requiring IV hydration uncontrolled by outpatient change in bowel habits with
medical
management, ileus or peritoneal signs and
requiring hospitalization or radiographic or biopsy
surgery
documentation
Grade IV Severe ulceration or requires Perforation or bleeding Perforation or requiring
parenteral or enteral nutrition requiring emergency surgery surgery or toxic megacolon
support or prophylactic
intubation
Leucovorin rescue guideline
Excretion
24 H MTX level
/Toxicity
Expected 24 H < 150 uM
excretion
Early delayed
>= 150 uM
excretion
and/or
>25% incrase Cr
and/or
Any mucositis
and/or
H/o of grade III-IV mucositis
or prolonged
myelosupression from
previous HD MTX course
48 H MTX level
Hydration/Leucovorin rescue
Maintain hydration at 125 ml/m2/h
Increase hydration to 200 ml/m2/h
10

Excretion
/Toxicity
Expected
excretion
24 H MTX level
48 H MTX level
Any MTX level
=< 0.4 uM
Grade I
Mild toxicity
Any MTX level

and/or
25-50% increase Cr
and/or
Grade I-II stomatitis
0.41-5.9 uM
and/or
25-50% increase Cr
and/or
Grade I-II stomatitis
Grade II
Moderate
toxicity
Any MTX level

and/or
50-100% increase Cr
and/or
On previous or current
course of HD MTX:
Grade III-IV stomatitis,
myelosupression
Any MTX level
and/or
>100% increase Cr
6-9.9 uM
and/or
50-100% increase Cr
and/or
On previous or current
course of HD MTX:
Grade III-IV stomatitis,
myelosupression
10-100 uM
and/or
>100% increase Cr
Any MTX level
>100 uM
Grade III
Severe Toxicity
Grade IV
Life threatening
Hydration/Leucovorin rescue
o LCV 15 mg/m2 at Hr 42, 48 and
54 then stop LCV
o No further MTX level required
o Increase hydration to 200 ml/m2/h
o LCV 15 mg/m2 at Hr 42, 48 and
54 then q 6 H PO/IV
o Recheck MTX level/ Cr q 24 H;
discontinue leucovorin when MTX
level < 0.1 uM or normalized of Cr
or resolved mucositis
o Start LCV 15 mg/m2 IV at Hr 42
then q 3 H IV
o Start LCV at 100 mg/m2 IV at Hr
42 then q 3 H IV
o Nephrology consultation
o Start LCV at 1000 mg/m2 IV at Hr
42 then q 3 H IV
level < 0.1 uM
o Nephrology consultation
11

Guide line for dose-modification of oral MTX and 6-MP in maintenance phase
Keep ANC between 500-1,500
o For low blood count:
ANC < 500 or PLT < 50,000: Held 6-MP and MTX until recovery
For first episode of ANC < 500 or PLT < 50,000; resume medication at same dose when
ANC > 500 and PLT > 50,000
For second episode of ANC < 500 or PLT <50,000;
o resume med at 50% dose when ANC > 750 and PLT > 75,000 (consider
changing bactrim to dapsone)
o Increase 6-MP and MTX to 75% and 100% at 4 week interval provided ANC >
750 and PLT > 75,000
Prolonged cytopenia defined as ANC < 500 and/or Platelet < 50,000 more than 4 weeks
Consider BM evaluation to rule out relapse
TPMT status evaluation: severe and unexpected myelosupression
o Prolonged cytopenia after rule out relapse
o Dont tolerate 50% dose of 6-MP and MTX
o For persistent ANC >= 1,500
ANC >= 1,500 for 2 consecutive month; alternate increase dose of MTX or 6-MP by 25%
If both MTX and MP are increased once without fall in ANC consider non-compliance
Check TPMT status
o Heterozygous or homozygous deficiency consider increase MTX by 25% in 4
weeks interval
o Homozygous WT consider increase 6-MP alternate with MTX by 25% in 4
weeks interval
o 6-MP dosing base on TPMT status
Homozygous WT: 75 mg/m2/day
Heterozygous: 60 mg/m2/day
Homozygous deficiency: 10 mg/m2/day 3 day per week
Mucositis grade 3-4
o Grade 3: MTX should be reduce to 50%
o Grade 4: MTX should be withhold until recovery then resume at 50% dose then gradual escalation
Liver dysfunction
o If SGOT and SGPT> 5xULN obtain TB/DB then follow level weekly
o Discontinue 6-MP and MTX if
DB > 2.0
SGOT/SGPT > 20x ULN on 2 determinations 1 week apart
o Consider infectious hepatitis (A,B,C) and other etiology (liver biopsy) if SGOT/SGPT above 5x ULN for
more than 4 weeks
Acute Lymphoblastic Leukemia (ALL): Guide line for dose-modification of oral MTX and 6-MP in
maintenance phase
12

Guidelines for Tyrosine Kinase Inhibitors administration
Available TKI in Thailand: Imatinib, Dasatinib, Nilotinib
Hematologic side effect
TKI should be held when patient dont make a count criteria to begin next phase of therapy, then
weekly CBC until patient make a count criteria for start the next phase. BM aspiration and biopsy should be
considered if treatment delayed more than 3 weeks. Do not hold TKI only for cytopenia during therapy.
Edema and effusion
TKI should be held for the following condition
o Pericardial effusion: effusion with physiologic consequence required intervention
o Ascites: severe symptoms, unresponsive to diuresis or required therapeutic paracentesis
o Peripheral edema: symptomatic edema limiting function, > 30% inter-limb discrepancy or
unresponsive to therapy
o Pleural effusion: symptomatic, requiring oxygen, intubation or therapeutic thoracocentesis
Hepatic toxicity
TKI can cause elevation of AST/ALT x 5-20 x ULN. Do not hold TKI for isolate AST/ALT elevation.
TKI should be held for
o AST or ALT > 20 x ULN
o Total bilirubin > 3 x ULN
o Prothrombin time > 2 x ULN
Cardiac toxicity
TKI should be held if
o Ejection fraction decline more than 20% from base line
o Shortening fraction < 24%
o Clinical congestive heart failure
Acute Lymphoblastic Leukemia (ALL): Guidelines for Tyrosine Kinase Inhibitors administration
13

Supportive care guideline
Infection prophylaxis and treatment:
Antibiotic Prophylaxis
Infection related mortality continues to be high during induction and delayed intensification. Follow
institutional policy for antimicrobial prophylaxis such as ciprofloxacin plus fluconazole during the high risk
phase.
Pneumocystis prophylaxis
PCP prophylaxis should be start as soon as possible after diagnosis of ALL and continue until 6
months after all therapy is completed.
o First line: Trimethoprin-sulfamethoxazole at 150/750 mg/m2/day (Max: 320 mg of
trimethoprim/day) in 2 divided doses on 3 consecutive days per week
o Second line options: Dapsone 2 mg/kg/day (Max: 100 mg/day) or aerosolized pentamidine
300 mg inhaled monthly or intravenous pentamidine 4 mg/kg/dose every 4 weeks
Fungal prophylaxis
Azole fungal agents given concurrently with vincristine may increase risk of neurotoxicity. Azole fungal
agent is potent inhibitor of CYP3A4/5 which can cause increase systemic exposure of TKI such as imatinib
and dasatinib.
Influenza immunization
Patient and household contacts should receive influenza immunization with trivalent inactivated
influenza vaccine.
Varicella infection and prophylaxis
Patient should be treated promptly with intravenous acyclovir and monitor for the development of
invasive systemic disease. Oral acyclovir for prophylaxis is recommended after completion of treatment.
Stress steroid support
If serious illnesses occur in close proximity to the completion of induction or delayed intensification,
consider additional stress steroid support.
Mucositis
Moderate (Grade 3) or severe (Grade 4) mucositis requires vigorous treatment including IV fluids,
hyperalimentation and strong consideration of braodspectrum antibiotics if febrile or appearing ill. Antiviral
therapy should be considered based on culture results and clinical evaluation. Do not proceed further HD MTX
or Doxorubicin until mucositis begin to heal.
Non radiation-mucositis grading
Antiemetic protection
Antiemetic should be given as needed. The routine use of steroids should be avoided.
Acute Lymphoblastic Leukemia (ALL): Supportive care guideline
14

Off therapy follow up guideline
End of therapy evaluation:
o Bone marrow aspiration, clot section or biopsy
o Echo or MUGA and EKG
o UA
o Electrolyte, calcium, magnesium, phosphate, BUN, Cr
o LFT
1st year off therapy:
o Follow up Q 1-2 months with CBC c diff
o Discontinue PCP prophylaxis at 6 months off therapy
o Echo or MUGA/ EKG at the end of therapy then as indicated
o AST/ALT Q 2 months until normal
o BUN/Cr, BMA and LP as clinically indicated
2nd year off therapy:
o Follow up Q 2 months with CBC c diff
3rd year off therapy:
4th year off therapy:
th
5 year off therapy and afterward
o Follow up annually with CBC c diff
o Follow long term survivor guideline
Age at diagnosis
1-4 y/o
XRT
Yes
No
>= 5 y/o
Yes
No
Anthracycline dose (mg/m2)

< 300
>= 300
< 100
100-299
>= 300
< 300
>= 300
< 200
200-299
>=300
Acute Lymphoblastic Leukemia (ALL): Supportive care guideline
ECHO(MUGA)/EKG interval (years)

1
1
5
2
1
2
1
5
2
1
15

Treatment protocol for standard risk acute lymphoblastic leukemia [Thai-POG ALL 1301]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia
[Thai-POG ALL 1301]
16

[Thai-POG ALL 1301]
17

[Thai-POG ALL 1301]
18

[Thai-POG ALL 1301]
19

[Thai-POG ALL 1301]
20

[Thai-POG ALL 1301]
21

Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high

standard
risk acute
lymphoblastic
leukemia
risk acute
lymphoblastic
leukemia
[Thai- 22
[Thai-POG
ALL 1301]
POG
ALL 1302]

Treatment protocol for high risk acute lymphoblastic leukemia [Thai-POG ALL 1302]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 23
POG ALL 1302]

POG ALL 1302]

POG ALL 1302]

POG ALL 1302]

POG ALL 1302]

POG ALL 1302]

Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia
[Thai-POG ALL 1303]
29

Treatment protocol for very high risk acute lymphoblastic leukemia [Thai-POG ALL 1303]
[Thai-POG ALL 1303]
30

[Thai-POG ALL 1303]
31

[Thai-POG ALL 1303]
32

[Thai-POG ALL 1303]
33

[Thai-POG ALL 1303]
34

[Thai-POG ALL 1303]
35

[Thai-POG ALL 1303]
36

[Thai-POG ALL 1303]
37

[Thai-POG ALL 1303]
38

Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute
lymphoblastic leukemia [Thai-POG ALL 1304]
39

Treatment protocol for Philadephia chromosome positive acute lymphoblastic leukemia [ThaiPOG ALL 1304]
40

41

42

43

44

45

46

47

48

49

50

51

52

Treatment protocol for relapsed acute lymphoblastic leukemia [Thai-POG ALL 1305]
Data entry form
Patients name......................................................... HN............................ Sex male female
Address......................................................................................................................................................................
..........................................................................Contact person....................................Tel........................................
Fathers name........................................................ Age...........yr Occupation.........................................
Mothers name........................................................ Age...........yr Occupation........................................
Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) ................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...............................................
History
Hx Risk factor :
Physical examination
Pedigree
Pre- treatment investigations.

A. Blood (//)
CBC ... Blast %
LDH ...
Immunophenotype (//) ....
Cytochemistry (//) ....
Cytogenetic (//) ....
Molecular study (//) ....
TPMT mutation(//) ......
Viral study HIV
Result positive Hepatitis profile ....
negative
CMV
Result positive.......
negative
EBV
Result positive.......
negative
B. Imaging study
Chest X-Ray (//) Result positive.... negative
C. Bone marrow for metastatic work up
Bone marrow aspiration*: (//)
Result positive
negative
LP (//)
Result positive
negative
Final diagnosis _________________________________________________
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia
[Thai-POG ALL 1305]
53

Treatment Protocol for Relapsed Acute Lymphoblastic Leukemia [Thai-POG ALL 1305]
Protocol name ThaiPOG-ALL-1305
Protocol for Relapsed Acute Lymphoblastic Leukemia
Open Date
January 2014
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
Inclusion criteria
Phase I INDUCTION (weeks 1-4)
week
day
Date given
Dexamethasone .................................... tab PO TID
Mitoxantrone ................................................... mg IV
Vincristine ....................................................... mg IV
L-asp............ U IM
MTX................................................................ mg IT*
BM aspiration remission not remission
MRD D29 Positive Negative Not done
Date start//
1
15
22
29
T#
T#
()
#Intrathecal chemotherapy for CNS 3 disease, to be given weekly until CSF ve for 2 consecutive times (at least 4 doses)
Drug
Dexamethasone
Dosage
20 mg/m2 /day PO/IV TID
Day
1-5 and 15-19
Mitoxantrone
10 mg/m2 IV
1, 2
Vincristine
1.5 mg/m2 IV push (max 2 mg)
3, 10, 17, 24
L-asparaginase
10,000 unit /m2 IM
3, 5, 7, 17, 19, 21
MTX IT*
age adjusted dose intrathecal
1, 8
* age adjusted dose intrathecal chemotherapy for Methotrexate

Age (year)
1-1.9 2-2.9
8
10
Total dose
>3
12
[Thai-POG ALL 1305]
54

Phase II CONSOLIDATION PHASE (weeks 5-8)
Date start//
Start consolidation phase on day 31, or when ANC > 750 and platelet > 75,000 (whichever occurs later)
5
6
7
8
week
1
8
15
22
day
Date given
Dexamethasone . tab PO BID
Vincristine ... mg IV push
Methotrexate . mg IV drip 24 hr
IIIIII
Leucovorin ... mg IV Q 6 hr
L-asp . UIM
xxxxx
Cyclophosphamide .. mg IV
+++++
Etoposide .. mg IV
MTX .. mg*
T
Drug
Dexamethasone
Dosage
6 mg/m2 day PO BID
Day
1-5
Vincristine (VCR)
1.5 mg/m2 IV push (max 2 mg)
Methotrexate
1,000 mg/m2 IV drip in 24 hr
Leucovorin
15 mg/m2 IV q 6 hr for 6 doses (start at hr 42 of MTX)
L-Asparaginase
10,000 unit /m2 IM
9, 11, 13
Cyclophosphamide
440 mg/m2 IV drip in 30 min
15-19
Etoposide
100 mg/m2 IV
15-19
MTX IT*

Age (year)
1-1.9 2-2.9
8
10
Total dose
>3
12
[Thai-POG ALL 1305]
55

Phase III INTENSIFICATION (weeks 9-12)
Start intensification phase when ANC > 750 and platelet > 75,000
9
week
1
day
Date given
Dexamethasone . tab PO BID
Vincristine ... mg IV push
Cytarabine . mg IV Q 12 hr
L-asp . UIM
Methotrexate . mg IV drip 24 hr
Leucovorin ... mg IV Q 6 hr
MTX .. mg*
T
Date start//
10
11
12
15
22
IIIIII
T
Drug
Dosage
Dexamethasone 6 mg /m2/day PO BID
Day
1-5
Vincristine
1.5 mg /m2IV push (max 2 mg)
Cytarabine
3,000 mg IV drip in 3 hr Q 12 hr
1,2 and 8, 9
L-Asparaginase
10,000 unit /m2 IM
Methotrexate
1,000 mg /m2 IV drip in 24 hr
2, 4, 9, 11,
23
22
Leucovorin
15 mg/m2 IV q 6 hr for 6 doses (start at hr 42 of MTX)
23
MTX IT*
1, 22

Age (year)
1-1.9 2-2.9
8
10
Total dose
>3
12
[Thai-POG ALL 1305]
56

Phase IV Before SCT
Start phase IV when ANC > 750 and platelet > 75,000
day
Date given
Fludarabine . mg IV drip daily
Cytarabine . mg IV Q 12 hr
Idarubicin .. mg IV
Date start//
1
See high dose MTX guideline
Drug
Fludarabine
Dosage
25 mg /m2 IV drip 1 hr OD
Day
1-5
Cytarabine
1,000 mg/m2 IV drip 3 hr OD
1-5
Idarubicin
10 mg/m2 IV drip in 0.5 hr
Total dose
[Thai-POG ALL 1305]
57

Phase V Before continuation I (weeks 14-21)
Date start//
Start before continuation I when ANC > 750 and platelet > 75,000 (whichever occurs later)
14
15
16
17
18
19
20
21
week
1
8
15
22
29
36
43
50
day
Date given
Dexamethasone ... tab PO BID
6-MP ..... tab PO hs
Vincristine ..... mg IV push
Methotrexate tab PO hs
Methotrexate tab PO Q 6 hr
Cyclophosphamide mg IV
x
x
Etoposide . mg IV
+
+
Cytarabine .. mg IV/SC daily

MTX .. mg*
T
T
Drug
Dexamethasone
Dosage
6 mg /m2 / day PO BID
Day
1-5 and 57-61
Total dose
6-mercaptopurine
75 mg/m2 PO hs
1-42 and 57-98
Vincristine
1.5 mg /m2 IV push (max 2 mg) 3, 59
Methotrexate
20 mg/m2 PO hs
10, 17, 31, 38, 67, 74, 88, 95
Methotrexate
25 mg/m2 PO Q 6 hr
22, 78
Cyclophosphamide 300 mg/m2 IV drip in 1 hr
42, 49, 99, 106
Etoposide
150 mg/m2 IV drip in 1 hr
42, 49, 99, 106
Cytarabine
50 mg/m2 IV/SC
43-46, 50-53, 100-103, 107-110
MTX IT*
1, 43, 57, 99

Age (year)
1-1.9 2-2.9
8
10
>3
12
[Thai-POG ALL 1305]
58

Phase V Before continuation II (weeks 22-29)
Start before continuation II when ANC > 750 and platelet > 75,000
22
23
24
week
57
64
71
day
Date given
6-MP ..... tab PO hs
Methotrexate tab PO Q 6 hr
Cyclophosphamide mg IV
Etoposide . mg IV
Cytarabine .. mg IV/SC daily
MTX .. mg*
T
Date start//
25
26
27
28
29
78
85
92
99
106
Drug
Dexamethasone
Dosage
6 mg /m2 / day PO BID
Day
1-5 and 57-61
Total dose
6-mercaptopurine
75 mg/m2 PO hs
1-42 and 57-98
Vincristine
1.5 mg /m2 IV push (max 2 mg) 3, 59
Methotrexate
20 mg/m2 PO hs
10, 17, 31, 38, 67, 74, 88, 95
Methotrexate
25 mg/m2 PO Q 6 hr
22, 78
Cyclophosphamide 300 mg/m2 IV drip in 1 hr
42, 49, 99, 106
Etoposide
42, 49, 99, 106
Cytarabine
50 mg/m2 IV/SC
43-46, 50-53, 100-103, 107-110
MTX IT*
1, 43, 57, 99

Age (year)
1-1.9 2-2.9
8
10
>3
12
[Thai-POG ALL 1305]
59

Phase VI CONTINUATION TREATMENT (weeks 30-104)
Start continuation treatment when ANC > 750 and platelet > 75,000
30
31
32
33
week
Date given
6-mercaptopurine tab PO hs
MTX .. mg*
Date start//
34
35
36
37
38
39
40
41
Drug
Dexamethasone
Dosage
6 mg /m2 / day PO BID every 4 weeks
Day
1-5
Vincristine
1.5 mg /m2 IV push (max 2 mg) every 4 weeks
6-mercaptopurine
75 mg/m2 PO hs daily
Methotrexate
20 mg/m2 PO hs weekly
MTX IT*
age adjusted dose Intrathecal (every 12 weeks)

Age (year)
1-1.9 2-2.9
8
10
Total dose
>3
12
[Thai-POG ALL 1305]
60

Treatment protocol for low risk infant acute lymphoblastic leukemia [Thai-POG ALL 1306]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 61
[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

[Thai-POG ALL 1306]

Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low

risk infanthigh
acuterisk infant acute
intermediate/
1307]
69

Treatment protocol for intermediate/ high risk infant acute lymphoblastic leukemia [Thai-POG ALL 1307]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute
70

71

72

73

74

75

76

77

78

79

80

Acute Myeloid Leukemia (AML): Treatment protocol for intermediate/ high risk infant acute lymphoblastic
leukemia [Thai-POG ALL 1307]
81

Acute Myeloid Leukemia (AML)

Risk stratification for AML
Low Risk (LR)
High Risk (HR)
Presence of low risk molecular marker: Inv 16, FLT3/ITD positive with high allelic ratio > 0.4
t(8,21) regardless of monosomy 5, monosomy 7,- regardless of low risk feature
5q, MLL-gene rearrangement or MRD status at Presence of monosomy 5, monosomy 7, -5q or
the end of induction-I
MLL rearrangement without low molecular risk
Normal cytogenetic with MRD < 0.1% at the end features
of induction-I
Normal cytogenetic with MRD >= 0.1% at the end
AML patient who has no molecular marker and of induction-I
cytogenetic information available
Induction failure (M2, M3 at the end of induction-I)
Definition:
Initial WBC: The first WBC at the treating institution, or the WBC prior to intravenous fluids, whichever
occurred first.
MRD: Minimal Residual Disease
AML diagnosis:
o BM show myeloblasts >= 20%, if clinically prohibited for BM aspiration or biopsy, peripheral
blood with myeloblasts >= 20% with adequate flow cytometry and cytogenetic can be
substituted for BM exam.
o BM show myeloblast < 20% with karyptypic abnormality characteristic for de novo AML such
as t(8;21), Inv(16). t(16;16) or 11q23 abnormalities or unequivocal presence of
magakaryoblasts
o Biopsy proved isolated myeloid sarcoma such as myeloblastoma, chloroma, leukemic cutis
CNS leukemia at diagnosis:
o Any number of blasts on cytospin prep in atraumatic (< 100 RBCs) lumbar puncture
o Clinical signs of CNS leukemia such as facial plasy, brain/eye involvement or hypothalamic
syndrome. Extra-ocular orbital masses are not considered CNS leukemia
o Radiographic evidences of intracranial, intradural mass consistent with chloroma
o Blasts in traumatic tap in which the WBC/RBC ratio in CSF is 2X more in the peripheral
blood
Steinherz/Bleyer algorithm for traumatic lumbar puncture:
Positive if CSF WBC/CSF RBC > 2 X Blood WBC/ Blood RBC
Bone marrow status:

o M1: < 5% myeloblasts
o M2: 5-19% myeoblasts
o M3: >= 20% myeloblasts
Acute Myeloid Leukemia (AML): Risk stratification for AML
82

Treatment schema
Protocol assignment for new AML patient:
New AML patient
No PML-RARa
PML-RARa
APL protocol
AML Induction-I
End of Induction evaluation
High Risk features

No
Yes
LR-AML protocol
HR-AML protocol
Treatment schema for AML protocol:

Induction-I
End of Induction evaluation
High Risk features
No
Yes
LR-Induction-II
HR-Induction-II
LR-Consolidation-I
HR-Consolidation-I
-Donor
LR-Consolidation-II
HR-Consolidation-II
+ Donor
HSCT
Treatment schema for APL protocol:

Induction
Consolidation#1
Consolidation#2
+/- Salavage RX
Maintenance
Acute Myeloid Leukemia (AML): Treatment schema
83

Allergy
Etoposide
Etoposide allergic reaction can be managed with pre-medication such as diphenhydramine 1 mg/kg
IV (max: 50 mg), ranitidine 1 mg/kg IV (max: 50 mg), hydrocortisone 1-4 mg/kg IV and by slowing the
infusion rate. Etoposide phosphate can be used as a substituted with the same dose and route.
Asparaginase
Local reaction (Inflammation at injection site, swelling)
o Continue administration in a presence of grade 1 allergic reaction such as transient flushing
or rash; drug fever < 38 C. Do not premedicate with anti-histamine; Premedication with
antihistamine may mask the appearance of anaphylactic reactions.
Anaphylaxis/Systemic allergic reaction (urticarial, wheezing, laryngospasm, hypotension, etc.)
o Discontinue asparaginase administration. Withdraw any subsequent asparaginase in the
protocol.
Cardiac toxicity
Idarubicin and Mitoxantrone
Anthracyclines will be withheld if there is a significant evidence of cardiac disease by ECHO or
MUGA (SF < 27%)
Do not restart anthracyclines if held for LV dysfuction which not associated with bacteremia or sepsis.
If LV dysfunction causes by bacteremia or sepsis, anthracyclines may be reinstituted once SF returned to
>= 27%
Hepatic toxicity
Asparaginase
L-Asparaginase is associated with hepatotoxicity but dosing guidelines for hepatic toxicity is not
available. Asparaginase administration during hepatic toxicity is at clinician discretion.
Idarubicin, Mitoxantrone, Etoposide
Dosing guideline for heaptic toxicity.
Resume full dose when direct bilirubin < 1.2 mg/dl
DB (mg/dl)
2-2.9
3-4.9
>= 5
Idarubicin
50% of calculated dose
Hold dose
Mitoxantrone
Hold dose
Etoposide
Hold dose
Acute Myeloid Leukemia (AML): Dose modification guidelines for chemotherapy toxicity
84

Neurotoxicity
Cytarabine
If patient have severe neurologic symptoms that interfere with daily life (>= grade 3 CTCAE) from
high dose cytarabine, omit further high dose cytarabine. The most common nervous sytem disorder is an
acute cerebellar syndrome with manifest as ataxia, nystagmus, dysarthria or dysmetria. However, seizures
and encephalopathy have also occurred following high dose cytarabine.
Pancreatitis
Asparaginase
Discontinue asparaginase in the presence of hemorrhagic pancreatitis or severe pancreatitis (Pain >
72 hours and amylase > 20 x ULN). Withhold further dose of asparaginase
Asparaginase can be given after mild pancreatitis only if symptoms and signs subside and amylas
level return to normal.
Renal toxicity
Cytarabine
Check CrCl before any high dose cytarabine (doses of 1,000 mg/m2 or greater)
If serum creatinin > 2 mg/dl or > 2 x normal of age, patient should be hydrate. Following hydration
patient must have CrCL >= 60 ml/min/1.73m2 to proceed with high dose cytarabine
If CrCl < 60 ml/min/1.73 m2, High dose cytarabine should be reduced from twice daily to once daily
dosing.
Etoposide
CrCl > 60 ml/min/1.73 m2 give full dose
CrCl 15-60 ml/min/1.73 m2 give 75% of calculated dose
CrCl < 15 ml/min/1.73 m2 consult nephrology.
Thrombosis
Asparaginase
Treat with appropriate antithrombotic therapy as indicated. For significant thrombosis which not line
related, consider evaluation for inherited predisposition to thrombosis.
APL differentiation syndrome
Clinical manifestation: patient usually present with cardiopulmonary distress which may devekop progressive
cardiopulmonary failure
At least 3 of the following criteria to diagnose
o Respiratory distress
o Hypoxemia
o Fever
o Erythematous rash
o Pulmonary infiltration
85

o Pleural or pericardial effusion
o CHF c impaired myocardial contractility
o Episodic hypotension
Management
Discontinue ATRA
Dexamethasone 0.25 mg/kg/dose (max 10 mg) IV or PO BID for 3 days, continue if sign and
symptom still persist.
Resume ATRA once all sign and symptoms resolve.
ATRA dose modification
Hepatotoxicity
Hold ATRA if AST or ALT >= 5 x ULN or bilirubin >= 3 x ULN
Restart ATRA at 75% of original dose when toxicity resolved. If PTC reoccurred, hold ATRA as above
then resume at 50% of original dose. If PTC recurred again discontinue ATRA and switch to other
therapy.
o Dose escalation to 75% dose and 100% dose may be attempt with during the next course of
therapy if there is no recurrence of toxicity
Pseudotumor cerebri (PTC)
Hold ATRA until symptoms improved
Restart ATRA at 75% of original dose. If PTC reoccurred, hold ATRA as above then resume at 50%
of original dose. If PTC recurred again discontinue ATRA and switch to other therapy.
Skin
Hold ATRA if patient develop symptomatic generalized erythroderma or macular, paupular or vesicle
eruption or desquamation covering >= 50% of body surface area.
Restart ATRA at 75% of original dose when toxicity resolved. If PTC reoccurred, hold ATRA as above
then resume at 50% of original dose. If PTC recurred again discontinue ATRA and switch to other
therapy.
o Dose escalation to 75% dose and 100% dose may be attempt with during the next course of
therapy if there is no recurrence of toxicity
86

Antiemetics
Corticosteriods should not be used as antiemetics or to prevent infusional toxicity of amphoteracin B.
Mucosal evaluation and care
Mucositis is expected to be severe, liberal use of pain medication is encouraged. Dental evaluation before
therapy is recommended.
Suppression of menstruation
Menstruating females may receive depo-provera during the entire course of therapy. Supression of mense
should be continued until platelet is 50,000 without transfusion support.
Infection prophylaxis
Pneumocystis prophylaxis
PCP prophylaxis should be start as soon as possible after diagnosis of AML and continue until 6 months
after all therapy is completed.
First line: Trimethoprin-sulfamethoxazole at 150/750 mg/m2/day (Max: 320 mg/day of trimethoprim) in
2 divided doses on 3 consecutive days per week
Second line options: Dapsone 2 mg/kg/day (Max: 100 mg/day) or aerosolized pentamidine 300 mg
inhaled monthly or intravenous pentamidine 4 mg/kg/dose every 4 weeks
Prevention of viral infection
Uses of leukoreduced blood product are strongly encouraged.
Prophylactic acyclovir can reduce recurrence of mucocutaneous HSV infection.
Prevention of bacteria and invasive fungal infection
Infection related mortality continues to be high during induction and consolidation. Follow institutional
policy for antimicrobial prophylaxis such as ciprofloxacin plus fluconazole (voriconazole, itraconazole or
posaconazole) during neutropenic phase after each chemotherapy cycle.
Acute Myeloid Leukemia (AML): Supportive care guideline
87

End of therapy evaluation:
Bone marrow aspiration, clot section or biopsy
Echo or MUGA and EKG
UA
Electrolyte, calcium, magnesium, phosphate, BUN, Cr
LFT
1st year off therapy:
Follow up Q 1 month for the first 6 months then Q 2 months for month 6-12 with CBC c diff
Discontinue PCP prophylaxis at 6 months off therapy
Echo or MUGA/ EKG at the end of therapy and month 7 then as indicated
AST/ALT Q 2 months until normal
BUN/Cr, BMA and LP as clinically indicated
2nd year off therapy:
Follow up Q 4 months with CBC c diff
3rd year off therapy:
Follow up Q 6 months with CBC c diff
4th year off therapy and afterward
Follow up annually with CBC c diff
Follow long term survivor guideline
Age at diagnosis
1-4 y/o
XRT
Yes
No
>= 5 y/o
Yes
No
Anthracycline dose (mg/m2)

< 300
>= 300
< 100
100-299
>= 300
< 300
>= 300
< 200
200-299
>=300
Acute Myeloid Leukemia (AML): Off therapy follow up guideline
ECHO(MUGA)/EKG interval (years)

1
1
5
2
1
2
1
5
2
1
88

Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 1301]
Protocol name: Thai-POG AML 1301
Reference:
COG AAML 1031
Protocol for: Low Risk AML
Total Pages: 5
Open date:
Jauary 2014
Patient eligibility:
Acute Myeloid Leukemia with
Presence of low risk molecular marker: Inv 16, t(8,21) regardless of Monosomy 5, 7, -5q, MLL-gene
rearrangement or MRD status at the end of induction
Normal cytogenetic with MRD < 0.1% at the end of induction-I
AML patients with no molecular marker and cytogenetic information available.
Patients name
Hospital
Disease Status:
Age
HN
BW
Sex
kg Ht
cm BSA
Treatment schema:
Initial WBC:
m2
Induction-I
FAB Morpholgy (M0-M7):

Immuno-phenotype:
End of Induction eval
CNS status (circle one):
Positive
Isolated Myeloid sarcoma (circle one): Yes
Negative
High Risk features
No
If yes, describe:
Cytogenetics:
FISH:
Mutation Status: FLT3
NPM1
CEBP-A
BMA (circle): M1
M2
M3
MRD (circle): Negative
Positive
End of Induction evaluation:
Imaging:
No
Yes
LR-Induction-II
HR protocol
LR-Consolidation-I
LR-Consolidation-II
Post induction risk assignment (check one):

Low Risk
High Risk: due to
End of therapy date:
Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML
1301]
89

Patients name
Age
Hospital
HN
BW
Phase I: INDUCTION-I (5 weeks)
Week
1
2
Day
1
8
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCCCCCC CCC
IDA
mg IV I I I
IT-ARA-C
mg T
(T)
(T) (T)
Investigation:
CBC/diff
CSF cell count/ cytospin
BUN, Cr, TB,DB, AST, ALT
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional)
Drug
Cytarabine (ARA-C IV)
IDArubicin (IDA)
Intrathecal Cytarabine
(IT ARA-C)
+
+
+
+
(+)
+
+
+
(+)
Sex
kg Ht
cm BSA
Date start:
4
5
22
28
29
3
15
(T)
+
+
+
(T)
(+)
+
+
+
Route
Dosage
IV over 30 minutes 100 mg/m2/dose Q 12 hours or
3.3 mg/kg/dose Q 12 hours if BSA < 0.6 m2
IV drip in 4 hours 12 mg/m2/dose once a day or
0.4 mg/kg/dose once a day if BSA < 0.6 m2
IT
Age(yrs )
Dose
0.-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
3
70 mg
m2
Start next
course
(InductionII) on day
29 or when
blood count
parameters
are met
Days
Days 1-10
Days 1,3,5
Day 1
Note
For CNS 3 patient: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatment.
Patient with refractory CNS leukemia following 6 dose of therapy will be manage according to
institutional protocol
For low risk patient: No need for HLA-typing
!!! For patient with no molecular or cytogenetics information available who treat according to
LR-AML protocol: If patient have available sibling(s), send HLA-typing from patient and all
siblings as soon as ANC > 500 and no visible peripheral blasts to find possible match related
donor to do HSCT after Consolidation-I
End of induction evaluation and post induction risk assignment for AML:
Low Risk
High Risk
Presence of low risk molecular marker: Inv 16,
FLT3/ITD + with high allelic ration > 0.4 regardless
t(8,21) regardless of Monosomy 5, 7, -5q or MRD
of low risk feature
status at the end of induction
Presence of monosomy 5, 7, -5q without low risk
Normal cytogenetic with MRD < 0.1% at the end of molecular marker
induction-I
of Induction-I
Induction failure (M2, M3 at the end of Induction)
1301]
90

Patients name
Hospital
Age
BW
HN
Sex
kg Ht
Phase II: LR-INDUCTION- II (4 weeks)
cm BSA
m2
Date start:
Begin on Day 29 of Induction-I. It is suggested but not required to have ANC > 1,000 cells/l and Platelets
> 75,000 cells/ l.
Week
Day
1
1
2
8
3
15
4
22
5
29
Date due
Date given
Medication:
ARA-C
IDA
IT-ARA-C
mg Q 12 H IV CCCCCCC
mg IV I I I
mg T (T)
C
(T)
(T)
(T)
(+)
+
+
+
(T)
Investigation:
CBC/diff
BM Aspiration
+
+
+

Drug
IDArubicin (IDA)
(IT ARA-C)
(+)
+
+
+
+
(+)
+
Start next
course
(Consolidation-I)
on day 29 or
when blood
count
parameters are
met
Route
Dosage
IT
Age(yrs )
Dose
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
3
70 mg
Days
Days 1-8
Days 1,3,5
Day 1
Note
For patient with CNS negative at diagnosis but develop CNS disease at the beginning of induction-II:
add twice weekly IT cytarabine until CNS is clear plus 2 additional treatments. Patient with refractory
CNS leukemia following 6 dose of therapy will be manage according to institutional protocol
1301]
91

Patients name
Hospital
HN
Phase III: LR- CONSOLIDATION -I (4 weeks)
Age
BW
Sex
kg Ht
Date start:
m2
cm BSA
Begin on Day 29 of Induction-II. It is suggested but not required to have ANC > 1,000 cells/l and Platelets
> 75,000 cells/ l.
Week
Day
Medication:
ARA-C
ETOP
IT-ARA-C
Investigation:
Date due
Date given
2
8
3
15
4
22
mg Q 12 H IV CCCCC
mg IV E EE EE
mg T
CBC/diff
BM Aspiration
CrCl if Cr> 2 mg/dl or 2 xULN
Drug
Cytarabine
(HD ARAC)
Etoposide (ETOP)
1
1
+
+
+
Start next
course
(ConsolidationII) on day 29 or
when blood
count
parameters are
met
+
+
Route
IV over 1-3 hours
IV over 60 -120 minutes
Intrathecal Cytarabine IT
(IT ARA-C)
5
29
Dosage
1,000 mg/m2/dose Q 12 hours or
33 mg/kg/dose Q 12 hours if BSA < 0.6 m2
150 mg/m2/dose once a day or
5 mg/kg/dose once a day if BSA < 0.6 m2
Age(yrs )
Dose
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
3
70 mg
Days
Days 1-5
Days 1-5
Day 1
Note
For patient with CNS negative at diagnosis but develop CNS disease at the beginning of
consolidation-I is considered CNS relapse.
Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of
HD-ARAC and continuing for 24 hours after the last dose.
For patient with no molecular or cytogenetics information available who treat according to
LR-AML protocol with available matched related donor:
o Consider HSCT after consolidation-I
1301]
92

Patients name
Age
Hospital
HN
BW
Phase IV: LR- CONSOLIDATION - II (4 weeks)
Sex
kg Ht
Date start:
cm BSA
m2
Begin on Day 29 of Consolidation-I. It is suggested but not required to have ANC > 1,000 cells/l and
Platelets>75,000 cells/ l.
Week
Day
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
MITOX _______ mg IV
IT-ARA-C _______ mg
1
1
2
8
3
15
4
22
5
29
End of
therapy
evaluation.
CCCC
MMMM
T
Investigation:
CBC/diff
BM Aspiration
Drug
Cytarabine
(HD ARAC)
MitoXANTRONE
(MITOX)
(IT ARA-C)
+
+
+
+
+
Route
IV over 1-3 hours
Dosage
IV over 15-30 minutes 12 mg/m2/dose once a day or
IT
Age(yrs )
Dose
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
3
70 mg
Days
Days 1-4
Days 3-6
Day 1
Note
End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, Elyte, CA,
Phos, BUN, Cr, AST/ALT, TB/DB.
1301]
93

Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 1302]
Protocol name: Thai-POG AML 1302
Reference:
COG AAML 1031
Protocol for: High Risk AML
Total Pages: 5
Open date:
January 2014
FLT3/ITD + with high allelic ratio > 0.4 regardless of low risk feature
Presence of monosomy 5, 7, -5q or MLL rearrangement without low risk molecular marker
Normal cytogenetic with MRD >= 0.1% at the end of Induction-I
Induction failure (M2, M3 at the end of Induction-I)
Patients name
Hospital
Disease Status:
HN
Age
kg Ht
BW
Initial WBC:
Sex
cm BSA
m2
Morphology: FAB (M0-M7):
CNS status (circle one): Positive
Immuno-phenotype:
Negative
Treatment schema:
No
If yes, describe:
Cytogenetics:
Mutation Status: FLT3
Induction-I
FISH
NPM1
HR features
CEBP-A
HR-Induction-II

BMA (circle):
M1
MRD (circle):
Negative
M2
M3
HR-Consolidation-I
Positive
Imaging:
-Donor
HR-Consolidation-II
Post induction Management (check one):
+ Donor
HSCT
HSCT donor available: HSCT after HR-Consolidation I

Donor type: (circle one) MRD
MUD
MUCB MMRD Haplo
HSCT donor not available: HR protocol chemotherapy

Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML
1302]
94

Patients name
Hospital
HN
Phase I: INDUCTION - I (5 weeks)
Week
1
Day
1
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCCCCCC
IDA _______ mg IV
I I I
IT-ARA-C _______ mg
T
(T)
Investigation:
CBC/diff
+
+
(+)
+
BM Aspiration
Drug
Cytarabine
(ARA-C IV)
IDArubicin (IDA)
(IT ARA-C)
Age
kg Ht
Date start:
4
22
28
BW
2
8
3
15
CCC
(T)
(T) (T)
+
+
+
+
(+) +
+
(T)
(+)
+
+
+
+
Route
Dosage
IT
Age(yrs )
Dose
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
3
70 mg
Sex
cm BSA
m2
5
29
Start next
course
(Induction-II)
on day 29 or
when blood
count
parameters
are met
Days
Days 1-10
Days 1,3,5
Day 1
Note
For CNS 3 patient: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatment.
Patient with refractory CNS leukemia following 6 dose of therapy will be manage according to
institutional protocol
In all High risk patients: HLA typing should be done from the patient and all available siblings as
soon as patients ANC > 500 and no evidence of peripheral blast. Activate donor search as soon as
possible in patient who have no match related donor to find any available donor for HSCT after
consolidation-I
End of induction evaluation and post induction risk assignment for AML:
Low Risk
High Risk
Presence of low risk molecular marker: Inv 16,
FLT3/ITD + with high allelic ration > 0.4
t(8,21) regardless of Monosomy 5, 7, -5q or MRD
regardless of low risk feature
status at the end of induction
Presence of monosomy 5, 7, -5q without low risk
Normal cytogenetic with MRD < 0.1% at the end molecular marker
of induction-I
of Induction-I
Induction failure (M2, M3 at the end of Induction)
Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 95
1302]

Patients name
Hospital
HN
Phase II: HR-INDUCTION - II (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Induction-I. It is suggested but not required to have ANC > 1,000 cells/l and Platelets
> 75,000 cells/ l.
Week
Day
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
MITOX _______ mg IV
IT-ARA-C _______ mg
Investigation:
1
1
2
8
CCCC
MMMM
T (T)
(T)
3
15
(T)
(T)
CBC/diff
4
22
(T)
5
29
Start next course

(Consolidation-I)
on day 29 or
when blood
count parameters
are met

BM Aspiration
ECHOor MUGA and EKG optional)
Drug
Route
Cytarabine
IV over 30 minutes
(ARA-C IV)
Mitoxantrone (MITOX) IV drip over 15-30
minutes
Intrathecal Cytarabine IT
(IT ARA-C)
Dosage
Days
1,000 mg/m /dose Q 12 hours or
Days 1-4
2
33 mg/kg/dose Q 12 hours if BSA < 0.6 m
Days 3-6
2
0.4 mg/kg/dose once a day if BSA < 0.6 m
Age(yrs )
Dose
Day 1
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
70 mg
3
2
Note
induction-II: add twice weekly IT cytarabine until CNS is clear plus 2 additional treatments. Patient
with refractory CNS leukemia following 6 dose of therapy will be manage according to institutional
protocol
Steroid eye drop 2 drops each eye Q 6 hours beginning immediately before the first dose of HDARAC and continuing for 24 hours after the last dose.
1302]
96

Patients name
Hospital
HN
BW
Phase III: HR- CONSOLIDATION - I (4 weeks)
Age
kg Ht
Date start:
Sex
cm BSA
m2
Begin on Day 29 of Induction-II. It is suggested but not required to have ANC > 1,000 cells/l and Platelets
> 75,000 cells/ l.
Week
Day
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
ETOP _______ mg IV
IT-ARA-C _______ mg
Investigation:
CBC/diff
BM Aspiration
1
1
2
8
3
15
4
22
CCCCC
E EE EE
T
+
+
+
5
29
Start next
course
(ConsolidationII or HSCT) on
day 29 or when
blood count
parameters are
met
+
+
+
Drug
Route
Cytarabine (HD ARAC) IV over 1-3 hours
Etoposide (ETOP)
(IT ARA-C)
IT
Dosage
Age(yrs )
Dose
0-0.99
20 mg
1-1.99
30 mg
2-2.99
50 mg
70 mg
3
Days
Days 1-5
Days 1-5
Day 1
Note
Post Consolidation-I treatment assignment:
o Any available HSCT donor: Proceed to HSCT
o No available HSCT donor: Continue consolidation-II
1302]
97

Patients name
Hospital
HN
BW
Phase IV: HR- CONSOLIDATION - II (4 weeks)
Age
kg Ht
Date start:
Sex
cm BSA
m2
Week
Day
1
1
2
8
CC
A
CC
A
3
15
4
22
5
29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
L-ASP _______ IU IM
Investigation:
End of therapy
evaluation.
CBC/diff
BM Aspiration
Drug
Route
Cytarabine
IV over 3 hours
(HD ARAC)
L-Asparaginase IM
(L-ASP)
Dosage
6,000 IU/m2/dose once a day or
200 IU/kg/dose once a day if BSA < 0.6 m2
Days
Days 1,2 and 8,9
Days 2 and 9. To be
given 6 hours after
the start of 4th and 8th
dose of ARA-C
Note
End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, Elyte, CA, Phos,
BUN, Cr, AST/ALT, TB/DB.
1302]
98

Optional treatment protocol for acute myeloid leukemia [Thai-POG AML-02-08]
Protocol name: TPOG AML-02-08
Protocol for:
Optional protocol for new patient diagnosed with AML
Open date:
January 2014
De novo Acute Myeloid Leukemia
Patients name
Hospital
Age
BW
HN
Total Pages: 8
Sex
kg Ht
cm BSA
m2
Disease Status:
Initial WBC:
Morphology: FAB (M0-M7):

Positive
Negative Immuno-phenotype:
Treatment schema:
No
Induction-I
If yes, describe:
Cytogenetics:
FISH
+/-Induction-II

BMA (circle):
M1
M2
M3
Consolidation-I
Imaging:
Consolidation-II
Post Induction Management (check one):

Match related HSCT donor available:
HSCT after Consolidation-II
- Donor
Consolidation-III
+ Donor
HSCT
Consolidation-IV
No Match related HSCT donor not available:

Complete AML chemotherapy
CNS treatment program:
YES
NO
Describe:
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML02-08]
99

Patients name
Hospital
HN
Phase I: INDUCTION (5 weeks)
Week
1
Day
1
Date due
Date given
Medication:
ARA-C _____ mg Q 24 H IV CCCCCCC
III
IDA _______ mg IV
TIT _______ mg
T
Age
BW
2
8
3
15
kg Ht
Date start:
4
22
Sex
cm BSA
28
Investigation:
CBC/diff
BM Aspiration
+
+
+
+
+
+
Drug
Route
IV over 24 hours
IDArubicin (IDA)
IV drip in 4 hours
Intrathecal Therapy
IT
Dosage
100 mg/m2/dose Q 24 hours or
Age(yrs )
MTX Ara-C HC
0-0.99
6 mg 15mg 6mg
1-1.99
8 mg 20mg 8mg
2-2.99
10 mg 30mg 10mg
3
12 mg 50mg 12mg
m2
5
29
Start next
course on
day 29 or
when
blood
count
parameters
are met
Days
Days 1-7
Days 1-3
Day 1
Note
For CNS disease patient: at diagnosis or during treatment, CNS therapy program will be
started at the end of consolidation IV. It will include brain radiation 1800 rad and spinal
radiation 1,200 rad.
If patient have available sibling(s), send HLA-typing from patient and all siblings as soon as
ANC > 500 and no visible peripheral blasts to find possible match related donor
End of induction treatment assignment for AML:
BM aspiration on day 28:
M1 start Consolidation-I
M2-M3 start Induction-II
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 100
02-08]

Patients name
Hospital
HN
Phase I/II: INDUCTION-II (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Induction-I regardless of blood count
Week
Day
Date due
Date given
Medication:
ARA-C _______ mg Q 24 H IV
IDA _______ mg IV
TIT _______ mg
Investigation:
CBC/diff
BM Aspiration
ECHOor MUGA and EKG (optional
Drug
IDArubicin (IDA)
Intrathecal Therapy
1
1
2
8
3
15
4
22
5
29
CCCCCCC
III
T
+
+
+
Start next course

(Consolidation-I)
on day 29 or
when blood
count parameters
are met
+
+
+
Route
IV over 24 hours
Dosage
100 mg/m2/dose Q 24 hours or
IT
Age(yrs )
MTX Ara-C
HC
0-0.99
6 mg 15mg
6mg
1-1.99
8 mg 20mg
8mg
2-2.99
10 mg 30mg
10mg
12 mg 50mg
12mg
3
Days
Days 1-7
Days 1-3
Day 1
Note
BM evaluation on day 28
o M-1: start next course of therapy (Consolidation-I) on day 29 or when blood count
parameter are met
o M-2, M-3: off protocol. Consider salvage therapy.
02-08]

Patients name
Hospital
HN
Phase II: CONSOLIDATION-I (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Induction-I or II. It is suggested but not required to have ANC > 1,000 cells/l and
Platelets > 75,000 cells/ l.
Week
Day
1
1
2
8
3
15
4
22
5
29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCC
ETOP
mg IV EEEE
TIT
mg T
Investigation:
CBC/diff
BM Aspiration
+
+
+
Start next course

(Consolidation-II)
on day 29 or
when blood count
parameters are
met
+
+
Drug
Route
Cytarabine (HD ARAC) IV over 1-3 hours
Etoposide (ETOP)
Intrathecal Therapy
IT
Dosage
Age(yrs)
MTX Ara-C HC
0-0.99
6 mg 15mg 6mg
1-1.99
8 mg 20mg 8mg
2-2.99
10 mg 30mg 10mg
12 mg 50mg 12mg
3
Days
Days 1-3
Days 2-5
Day 1
Note
02-08]

Patients name
Hospital
HN
Phase III: CONSOLIDATION-II (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Week
Day
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
L-ASP _______ IU IM
TIT_______ mg
Investigation:
CBC/diff
BM Aspiration
1
1
2
8
CC
A
T
CC
A
+
+
+
4
22
5
29
Start next
course
(ConsolidationIII or HSCT) on
day 29 or when
blood count
parameters are
met
+
+
Drug
Cytarabine
(HD ARAC)
L-Asparaginase
(L-ASP)
Route
IV over 3 hours
Intrathecal Therapy
IT
IM
3
15
Dosage
6,000 IU/m2/dose once a day or
Age(yrs )
0-0.99
1-1.99
2-2.99
3
MTX
6 mg
8 mg
10 mg
12 mg
Ara-C
15mg
20mg
30mg
50mg
HC
6mg
8mg
10mg
12mg
Days
Days 1,2 and 8,9
Days 2 and 9. To
be given 6 hours
after the start of
4th and 8th dose
of ARA-C
Day 1
Note
End of consolidation-II treatment assignment:
o Available match related donor HSCT
o No available match related donor continue consolidation-III
02-08]

Patients name
Hospital
HN
Phase IV: CONSOLIDATION-III (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Consolidation-II. It is suggested but not required to have ANC > 1,000 cells/l and
Platelets > 75,000 cells/ l.
Week
Day
1
1
2
8
3
15
4
22
5
29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
ETOP _______ mg IV
TIT _______ mg
CCC
EEEE
T
Investigation:
CBC/diff
BM Aspiration
Drug
Cytarabine
(HD ARAC)
Etoposide
(ETOP)
Intrathecal Therapy
+
+
+
+
+
Route
IV over 1-3 hours
IT
Start next course

(Consolidation-IV)
on day 29 or when
blood count
parameters are met
Dosage
Age(yrs )
MTX
Ara-C HC
0-0.99
6 mg
15mg 6mg
1-1.99
8 mg
20mg 8mg
2-2.99
10 mg
30mg 10mg
12 mg
50mg 12mg
3
Days
Days 1-3
Days 2-5
Day 1
Note
02-08]

Patients name
Hospital
HN
Phase V: CONSOLIDATION-IV (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/l and
Week
Day
1
1
2
8
CC
A
T
CC
A
+
+
+
+
+
3
15
4
22
5
29
End of therapy
evaluation or
CNS treatment
program for CNS
disease patient
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV
L-ASP _______ IU IM
TIT _______ mg
Investigation:
CBC/diff
BM Aspiration
+
+
Drug
Cytarabine
(HD ARAC)
L-Asparaginase
(L-ASP)
Route
IV over 3 hours
Intrathecal Therapy
IT
IM
Dosage
6,000IU/m2/dose once a day or
Age(yrs )
0-0.99
1-1.99
2-2.99
3
MTX
6 mg
8 mg
10 mg
12 mg
Ara-C
15mg
20mg
30mg
50mg
HC
6mg
8mg
10mg
12mg
Days
Days 1,2 and 8,9
Days 2 and 9. To
be given 6 hours
after the start of
4th and 8th dose
of ARA-C
Day 1
Note
End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, Elyte, CA, Phos,
BUN, Cr, AST/ALT, TB/DB.
02-08]

Patients name
Hospital
HN
Age
kg Ht
BW
Phase VI: CNS- Treatment program (for CNS disease patient only)
Sex
cm BSA
m2
Date start:
Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/l and
Radiation field
:(
Total radiation dose
:(
Number of fractions
:(
Date start
:(
Last day of radiation
:(
CT date
:(
Note
End of therapy evaluation should be done 8 weeks after complete radiation therapy: CBC,
MUGA/ECHO, BMA/clot section or biopsy, UA, Elyte, CA, Phos, BUN, Cr, AST/ALT, TB/DB, CT or
MRI brain for intracranial cholroma patient.
02-08]

Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 0106]
Protocol name: Thai-POG APL 0106
Reference:
PETHEMA LPA-99 study
Protocol for:
Acute Promyelocytic Leukemia
Total Pages: 5
o PML/RARa fusion gene from PCR, FISH or cytogenetic
Patients name
Hospital
Disease Status:
Initial WBC:
HN
Age
Sex
kg Ht
cm BSA
Treatment schema:
BW
FAB Morpholgy (M0-M7):
m2
Induction
Immuno-phenotype:
Positive
Negative
Isolated Myeloid sarcoma (circle one):
Yes
Day#45 evaluation
N
No
Remission
If yes, describe:
Cytogenetics:
FISH:
No

Day 45 BMA (circle):
M1
M2
M3
ATRA; Max 90
days
Imaging:
Duration of ATRA
days
Remission status from day 45-90:
PML/RARa positive Salvage therapy: date
Consolidation#1
Remission
No
Maintenance
No
PML/RARa negative Maintenance: date

PML/RARa positive Off protocol
/
PML/RARa fusion
No
Post Salvage therapy
Consolidation#2
Yes
Post Consolidation treatment assigment (check one):

PML/RARa negative Maintenance: date
Yes
Off protocol
Yes
Yes
Salvage Rx
PML/RARa fusion
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL
0106]
107

Patients name
Hospital
HN
BW
Phase I: INDUCTION- (6-13 weeks)
1
2 3 4 5 6 7 8
Week
1
15
36 45
Day
Date due
Date given
Medication:
ATRA _______ mg Q 12 H PO
IDA _______ mg IV
Investigation:
CBC/diff
BM Aspiration
Age
kg Ht
Date start:
9 10 11
57
III
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
12
78
Sex
cm BSA
m2
90
Start next
course
(consolidation)
on day 46 or
when BM show
remission or
when blood
count
parameters are
met
+
+
+
+
+
Days
Days 1-Remission
Days 1,2,3
Drug
Route
Dosage
All-Trans-Retinoic-Acid (ATRA)
PO
25 mg/m2/day BID
IDArubicin (IDA)
IV drip in 4 hours 10 mg/m2/dose once a day
Note
Continue ATRA until morphologic remission, maximum duration of 90days
Bone marrow aspiration on day 45
o In remission start consolidation therapy
o Not in remission continue ATRA and repeat BMA periodically until remission (no
more than 90 days) then start consolidation after remission
o If patient is not in remission after 90days, consider switch to protocol which contain
Arsenic.
Keep fibrinogen > 150 mg/dl and platelet count > 30,000-50,000/mm3 if patients develop sign of
coagulopathy
Please see APL differentiating syndrome (ATRA syndrome) criteria for diagnosis and
management guideline in Thai-POG AML management guideline
0106]
108

Patients name
Hospital
HN
Phase II: Consolidation- (8 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 46 of Induction or when in remission. It is suggested but not required to have ANC > 1,000
cells/l and Platelets > 75,000 cells/ l.
Week
Day
Date due
Date given
Medication:
ATRA _______ mg Q 12 H PO
IDA _______ mg IV
Investigation:
CBC/diff
BM Aspiration
1
1
Cycle 1 /Cycle 2
/
2
8
3 3
15 16
4
22
I I I
+
+
+
+
5
29
Start consolidation
cycle 2 on day 29
of consolidation
cycle 1.
Start Next course
(Salvage therapy
or maintenance)
on day 29 of
consolidation cycle
2
Drug
Route
Dosage
Days
2
All-Trans-Retinoic-Acid PO
25 mg/m /day BID
Days 1-15
(ATRA)
IDArubicin (IDA)
IV drip in 4 hours
10 mg/m2/dose once a day
Days 1-3
Note
Consolidation therapy consisted of 2 cycle. Each cycle should be given every 4 weeks
Evaluate PML/RARa fusion gene after the end of Consolidation cycle#2
o PML-RARa negative start maintenance phase
o PML-RARa positive Start Salvage therapy
Cycle#1 date start
Cycle#2 date start
/
/
/
/
Post consolidation PML/RARa fusion gene (circle one):
Positive
Negative
0106]
109

Patients name
Hospital
HN
Phase III: Salvage Therapy- (4 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin after Day 29 of Consolidation cycle#2. It is suggested but not required to have ANC > 1,000 cells/l
and Platelets > 75,000 cells/ l.
Week
Day
Date due
Date given
1
1
Medication:
ARA-C _______ mg Q 12 H IV
Investigation:
CCC
CBC/diff
+
+
BM Aspiration
+
+
Drug
Cytarabine (HD ARAC)
Route
IV over 1-3 hours
2
8
+
+
3
15
+
+
4
22
+
+
Dosage
5
29
Start next
course
Maintenance on
day 29 or when
blood count
parameters are
met
Days
Days 1-3
Note
Salvage therapy is given only in patient whose PML/RARa fusion gene still positive after the
end of consolidation phase
Evalaute PML/RARa fusion gene after complete salvage therapy
o PML/RARa negative start maintenance phase
o PML/RARa positive off protocol. Consider other salvage regimen.
0106]
110

Patients name
Hospital
HN
Phase IV: Maintenance- (12 weeks)
Age
kg Ht
Date start:
BW
Sex
cm BSA
m2
Begin on Day 29 of Consolidation cycle#2 or Salvage therapy. It is suggested but not required to have ANC
> 1,000 cells/l and Platelets>75,000 cells/ l. Repeat maintenance therapy for total of 8 cycle.
Week
Day
Medication:
1
1
ATRA______ mg po BID
6-MP _____ mg PO daily
MTX _______ mg PO
CBC/diff
+
+
Investigation:
2
8
3 3
15 16
4 5 6
22 29 36
7 8
43 50
9 10
57 64
11 12 13
71 78 85
Repeat
next cycle
for total of
8 cycles
Drug
Route
Dosage
Days
All-Trans-Retinoic-Acid (ATRA)
PO
25 mg/m2/day BID
Days 1-15
PO
6-Mercaptopurine (6-MP)
50 mg/m2/dose
Day 1-84
2
PO
Methotreaxate (MTX)
20 mg/m /dose
Day 1 then weekly until Day 78
Note
6-MP and MTX should be hold when ANC < 500 or Plt < 50,0000.
6-MP and MTX should be restarted when ANC > 750 and Plt > 75,000
First time discontinuation: restart at full dose
Second time discontinuation and after: restart at 50% dose reduction. Slowly escalate dose
by 25% in 2-4 week interval until reach original dose if ANC > 750 and Plt > 75,000
Recommend BM evaluation and TPMT gene mutation evaluation for oatient with prolong
cytopenia more than 4 weeks
Cycle
Date
given
BSA
Medication dosage
Weight ______ kg
Height ______ cm
BSA _______ m2
ATRA ________ mg po BID

6-MP _________ mg po daily
MTX ________ mg po weekly
Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Weight ______ kg
Height ______ cm
BSA _______ m2

Note:
0106]
111

Lymphoma
Hodgkin disease
Risk stratification
Low risk (LR)
Stage I-A with no bulk
Stage II-A with no bulk
Intermediate Risk (IR)

Stage I-E, I-B and I-A with bulk
Stage II-E, II-B and II-A with bulk
Stage III-A
Stage IV-A
High Risk (HR)

Stage III-B
Stage IV-B
Definition:
Stage grouping
Stage I Involvement of single lymph node region (I) or localized involvement of a single extra
lymphatic organ or site (IE)
Stage II Involvement of 2 or more lymph node regions on the same side of diaphragm (II) or localized
contiguous involvement of a single extralymphatic organ or site and its regional lymph nodes(s) with
involvement of 1 or more lymph node regions on the same side of the diaphragm (IIE).
Stage III Involvement of lymph node regions on both sides of the diaphragm (III), which may also
accompanied by localized contiguous involvement of an extralymphatic organ or site (IIIE), by involvement of
the spleen (IIIS) or both (IIIE+S).
Stage V Disseminated involvement of 1 or more extralymphatic organs or tissues, with or without
associated lymph node involvement, or isolated extralymphatic organ involvement with distant nodal
involvement
Symptoms and presentation
A Symptoms: lack of B symptoms.
B Symptoms: At least one of the following:
Unexplained weight loss > 10% in the preceding 6 months;
Unexplained recurrent fever > 38 C in the preceding months;
Recurrent drenching night sweats in the preceding month
Bulk disease
Large mediastinal mass: Tumor diameter > 1/3 of thoracic diameter on upright PA CXR.
Large extra-mediastinal nodal aggregate: A continuous aggregate of nodal tissue that measures > 6 cm
in the longest transverse diameter in the axial plane in any nodal area.
Macroscopic splenic nodules: focal defect in the spleen seen on CT, PET or MRI imaging studies
consistent with Hodgkin lymphoma will be deemed to be bulk disease
Lymphoma: Hodgkin disease
112

Number of regions of nodal involvement
Each of these 20 regions is counted separately for purpose of determining clinical group.
Peripheral regions
Central regions
Lower regions
Rt neck; cervical,
Waldeyers ring (include
Rt iliac
supraclavicular, occipital, prebase of tongue)
Lt iliac
auricular
Mediastinum (include
Rt inguinal and femoral
Lt neck; cervical,
paratracheal)
Lt inguinal and femoral
supraclavicular, occipital, pre- Hilar
Rt popliteal
auricular
Mesenteric
Lt popliteal
Rt infraclavicular
Paraaortic (include
Lt infraclavicular
retrocrural, portal and celiac)
Rt axilla and pectoral
Splenic/splenic hilar
Lt axilla and pectoral
Rt epitrochlear and brachial
Lt epitrochlear and brachial
113

Clinical criteria for nodal involvement
Upper torso
Any node with longest transverse diameter > 1.5 cm
Cervical or axillary node may reach >= 2 cm in the longest diameter on physical exam, USG, CT or
MRI before being considered if reactive hyperplasia is considered possible
Any cluster of matted or adherent nodes
Any enlarged supraclavicular nodes
Any mediastinal adenopathy
Any FDG-positive nodes
Lower torso
Any node with longest transverse diameter > 1.5 cm
Inguinal and mesenteric node may reach >= 2 cm in the longest diameter on physical exam, USG,
CT or MRI before being considered if reactive hyperplasia is considered possible
Any FDG-positive nodes, liver or spleen
A spleen or liver that has focal defect on imaging
Response criteria
Measurable lesions up to the maximum of 6 lesions in total will be measured as a target lesion at base
line and followed for response
Lesion size is expressed as the product of perpendicular diameter (PPD)
PPD is obtained by multiply the longest diameter of the lesion by maximal diameter perpendicular to the
longest diameter (multiply of the two longest diameter from imaging)
PPD = surrogate measurement of are with dimension of cm2
PET result
CT result
Negative
-Complete disappear of all target nodal mass or mass of any size

- At least 80% reduction in sum of PPD of up to 6 largest nodal
mass including mediastinum and return to normal size with no
residual mass greater than 2 cm
-At least 80% reduction in sum of PPD of up to 6 largest nodal
Negative
Positive
Positive
Positive
Positive

- At least 80% reduction in sum of PPD of up to 6 largest nodal
Less than complete disappearance but greater than 50% reduction
in sum of PPD of up to 6 of largest nodal masses.
Less than 50% reduction or less than 50% increase in sum of PPD
of up to 6 of largest nodal masses with no new lesions.
Greater than 50% increase in PPD of any of the nodal masses or
development of new measurable lesion
Nodular splenic
involvement
Negative
RESPONSE
Positive
Partial response
Not applicable
Partial Response
Not applicable
Partial Response
Not applicable
Stable Disease
Not applicable
Progressive
Disease
Complete
Response
114

Treatment schema
Hodgkin Disease
Intermediate risk
Low risk
ABVE x 2 cycle
High risk
ABVE-PC x 2 cycle
CT/PET/Gal
CT/PET/Gal
CR
PR/SD
PR/SD (SER)
CR (RER)
ABVE x 2 cycle
ABVE x 2 cycle
MIED x 2 cycle
ABVE-PC x 2 cycle
CT/PET/Gal
CT/PET/Gal
CT/PET/Gal
IFRT
CR
Follow up
CR
ABVE-PC x 2 cycle
PR/SD/PD
CT/PET/Gal
PD
PD
Salvage protocol
SD/PR/CR
PR
IFRT
CR
Follow up
Note
CR = complete remission, PR= partial remission, SD = stable disease, PD = progressive disease

ABVE = Doxorubicin + Bleomycin + Vincristine + Etoposide
ABVE-PC = Doxorubicin + Bleomycin + Vincristine + Etoposide Prednisolone + Cyclophosphamide
MIED = High dose methotrexate + Etoposide + Ifosphamide + dexamethasone
IFRT = Involved field irradiation therapy
Gal: Gallium scan
CT is a standard for re-evaluation imaging, PET and Gal are optional for re-evaluation imaging
Lymphoma: Treatment schema
115

ABVE and ABVE-PC regimen:
o Hematologic Toxicity
Full dose of chemotherapy should begin on day 22 if ANC >= 750/ul (with patient off G-CSF for
at least 2 days before next cycle) and platelets are >= 75,000/uL. If a patient has not recovered
by day 21, check CBC twice weekly and begin chemotherapy as soon as hematologic recovery.
o Hepatic toxicity
If bilirubin > 1.5 x ULN when chemotherapy is due to be given, hold chemotherapy and check
bilirubin twice weekly until it is < 1.5 x ULN.
o Hematuria
Microscopic hematuria
Transient microscopic hematuria (=< 2 abnormal UA on 2 separate days during cycle of
chemotherapy): Do not modify cyclophosphamide dose. Increase hydration (3,500 -4,000
ml/m2/day) and use total daily MESNA dose equal to 60% of daily cyclophosphamide dose.
Persistent microscopic hematuria (> 2 abnormal UA during a cycle of therapy): Do not modify
the cyclophosphamide dose. Increase hydration (3,500 -4,000 ml/m2/day) and use total daily
MESNA dose equal to 100% of daily cyclophosphamide dose.
o Gross hematuria
All episode of gross hematuria should be evaluated in conjunction with pediatric urology
consultation.
Transient gross hematuria (only 1 episode which clear to less than gross hematuria): During or
following a cycle of therapy, Hold cyclophosphamide until hematuria clears. When hematuria
clears, restarted at 50% of previous cyclophosphamide dose. Use hydration 3,500-4,000
ml/m2/day and MESNA at 100% of cyclophosphamide dose as a continuous drip over 24 hours.
The cyclophosphamide dose may be escalated back to 100%, if tolerated, and mesna give at
100% as continuous drip.
Persistent gross hematuria: after completion of a cycle of therapy, hold subsequent
cyclophosphamide doses until the urine clears to less than gross hematuria. When hematuria
clears, restarted at 50% of previous cyclophosphamide dose. Use hydration 3,500-4,000
ml/m2/day and MESNA at 100% of cyclophosphamide dose as a continuous drip over 24 hours.
The cyclophosphamide dose may be escalated back to 100%, if tolerated, and mesna give at
100% as continuous drip.
For persistent or recurrent gross hematuria on the mesna continuous drip: Discontinue
subsequence cyclophosphamide dose.
o Pulmonary
If DLCO in any diffusion capacity test is < 50% of the initial value or predicted value or if both
DLCO and FEV/FVC show rapid parallel decrease, obtain blood gases, discontinue further
bleomycin.
Lymphoma: Dose modification guidelines for chemotherapy toxicity
116

o Cardiac
If SF < 28% or EF < 50% on 2 study at least 1 week apart, the doxorubicin should be held
If patient develop sign and symptoms of congestive heart failure or prolong QTc which are not
attribute to other causes such as sepsis or renal failure, hold doxorubicin and perform
ECHO/MUGA and EKG prior to next planned dose.
o Peripheral neurotoxicity
Vincristine should be held or reduced only for incapacitating peripheral neurotoxicity. Vincristine
can be resumed when the symptoms have improved or completely resolved. If held, the
subsequent dose will be given at 25% dose reduction (Max: 2.1 mg)
o Hypersensitivity reaction to Etoposide
Discontinue Etoposide infusion if patient exhibit hypersensitivity reaction relate to infusion.
If additional dose of etoposide are scheduled to complete therapy
Consider Etoposide phosphate substitution with premedication. If Etoposide phosphate

is not available, continue further therapy with Etoposide with lower rate of infusion.
Premedication:
o Prednisone 1 mg/kg/dose
o Diphenhydramine 1 mg/kg/dose (Max: 50 mg)
o Hypersensitivity reaction to Bleomycin
Discontinue Bleomycin infusion if patient exhibit hypersensitivity reaction relate to infusion
If additional dose of Bleomycin are scheduled to complete therapy
MIED regimen:
Methotrexate
Toxicity
Myelosuppression
Mucositis, Severe
abdominal pain,
Diarrhea
Continue further therapy with Bleomycin with lower rate of infusion.

Premedication:
o Prednisone 1 mg/kg/dose
o Diphenhydramine 1 mg/kg/dose
Grade
On day 1 of each cycle:
ANC < 750 or Plt <
75,000
Grade 3 (painful
erythema, edema or
ulcers requiring IV)-Grade
4 (severe ulceration,
required parenteral
nutrition or intubation) or
diarrhea
Action
Delayed until recovery
Consider Leucovorin rescue adjustment: see MTX

infusion guideline
117

Toxicity
Renal toxicity
Abnormal LFTs
Grade
GFR < 70 ml/min/1.73m2
Not MTX induced
LFT elevated
Action
Delay until recovery
MTX induced (up to 3

weeks after MTX)
High dose MTX can cause hyperbillirubinemia and

transaminitis that last up to 2 weeks that will not be
consider toxicity required discontinuation of the
drug
Bilirubin > 1.5x ULN
Persistent hyperbillirubinemia for longer than 3

weeks will result in discontinuation of MTX
Delayed 1 week. Give if ALT < 10x ULN
Ifosphamide/Etoposide
Toxicity
Grade
Myelosuppression
On day 1 of cycle: ANC < 750
or Plt < 75,000
Mucositis
Grade 4 (severe ulceration,
require TPN or intubation) after
previous cycle or repeated
Grade 3 (painful erythema,
edema or ulcer requiring IV)
Renal toxicitySerum Cr > 1.5 x baseline or
Glomerular
GFR < 70 ml/min/1.73 m2
Renal toxicityTubular
Action
Delayed until recovery
Reduce ETOP by 50%
Delay for 1 week. If renal function does not

improve, discontinue IFOS, confirm GFR and
consider substituting Cyclophosphamide and
MESNA at 500 mg/m2 x 5 days
FR 10-50 ml/min/1.73 m2
Reduce ETOP by 25%
GFR < 10 ml/min/1.73 m2

Grade 1 (asymptomatic)
Reduce ETOP by 50%

No change
Grade 2 (mild, reversible,

manageable with oral
replacement)
Consider reduction of IFOS by 20%
Grade 3 (reversible but require No further IFOS. Consider substituting

IV replacement) or 4
cyclophosphamide and MESNA at 500 mg/m2
(irreversible require continued x 5days
replacement)
118

Toxicity
Hematuria
Neurological
Toxicity- Confusion,
alteration of level of
consciousness
Neurological
Toxicity- Seizure
Grade
Dipstick positive prior to IFOS
Action
Give additional MESNA bolus of 600 mg/m2
then continuous infusion at double dose
Microscopic during IFOS >= 2

episode (> 50 RBC/HPF)
No further IFOS. If hematuria resolves

completely, IFOS with double dose MESNA
could be consider with the next cycle or
consider substituting cyclophosphamide and
MESNA at 500 mg/m2 x 5days
>= Grade 2 (intermittent gross

hematuria with no clot);
excludes other cause; double
dose MESNA +/- increase
hydration
Grade 2 (confusion or
disorientation or attention
deficit or somnolence or sedate
interfering function but not daily
living)
Discontinue IFOS, continue double dose

MESNA and hydration for 24 hours after
IFOS. For the next cycle consider
cyclophosphamide and MESNA at 500 mg/m2
x 5days
No change unless persistent or distressing.
Then decrease IFOS by 20%. If persists,
reduce by a further 20%.
Grade 3 (confusion or delirium

or obtundation or stupor;
difficult to arouse, interfering
with daily living)
Stop IFOS for this cycle. Decrease IFOS by

20% during next cycle. If persists, reduce by
a further 20%.
Grade 4 (harmful to others or

self, require hospitalization or
coma)
Stop IFOS for this cycle and no further IFOS.

Give methylene blue at 2 mg/kg (Max: 50
mg). The dose can be repeated at 4 hours
and 8 hours after. Hypersensitivity, renal
impairment and G-6PD deficiency are
contraindications for methylene blue.
Substituting IFOS with cyclophosphamide and
MESNA at 500 mg/m2 x 5days for next cycle.
Stop IFOS for this cycle. Continue future
cycle at the same dose.
Grade 2 (self-limited and

consciousness is preserved)
Grade 3 (consciousness is
altered)
Stop IFOS for this cycle. Continue future

cycle at the same dose with anticonvulsant
coverage.
119

Toxicity
Grade
Grade 4 (prolong, repetitive or
difficult to control)
Neurological
Toxicity-peripheral
neuropathy
>= Grade 2 (objective

weakness or sensory loss or
paresthesia but not interfere
with daily living)
Action
Stop IFOS for this cycle and no further IFOS.
Give methylene blue at 2 mg/kg (Max: 50
mg). The dose can be repeated at 4 hours
and 8 hours after. Hypersensitivity, renal
impairment and G-6PD deficiency are
contraindications for methylene blue.
Substituting IFOS with cyclophosphamide
and MESNA at 500 mg/m2 x 5days for next
cycle.
Omit further IFOS. For the next cycle
consider cyclophosphamide and MESNA at
500 mg/m2 x 5days.
Dexamethasone
Hypertension: Doses should not be reduced. Sodium restriction and anti-hypertensive should be employed.
Avoid calcium channel blockers due to prohemorrhagic effect.
Hyperglycemia: Dose should not be reduced for hyperglycemia. Insulin therapy should be employed to
control blood sugar.
Pancreatitis: Discontinue steroid in a presence of severe or hemorrhagic pancreatitis.
Osteonecrosis: Do not modify steroid therapy during treatment.
Varicella: Steroids should be held during active infection except during induction.
Inability to use oral doses:
Dexamethasone: substitute the IV preparation mg for mg
Prednisone: Substitute IV methylprednisone at 80% of oral prednisone dose.
o Severe infection: Do not hold or discontinue steroid during induction. Later in therapy, one
may consider holding steroid until patient cardiovascular stability. Except stress doses.
o Sever psychosis: Dexamethasone dose may reduce by 50% for severe psychosis. If
symptoms persist, switch to prednisone.
High dose methotrexate infusion guideline
HD MTX administration
Hold bactrim, NSAID, penicillins, PPI or aspirin containing medication on the day of IV MTX infusion
and for at least 72 hours after start MTX infusion.
Hours -6 to 0: D5W+40-60 mEq NaHCO3/L+ 10 mEq KCL/L at 200 ml/m2/h to achieve urine pH 7-8
Hours 0 to 4: Methotrexate 8 g/m2 (Max: 20 grams) in 500 ml/m2 D5W +40 mEq NaHCO3/L+ 10 mEq
KCL/L at 125 ml/m2/h IV over 4 hours. All doses should be round up to the next highest full gram
value.
Lymphoma: High dose methotrexate infusion guideline
120

Hours 4 to 54: Post-hydration with D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h.
Hour 24: Begin leucovorin 15 mg/m2 PO/IV Q 6 hours. Beginning at T=24h (from the beginning of
MTX infusion) and continue until serum MTX is < 0.1 uM or until delayed excretion criteria is reached.
Laboratory monitoring
MTX level and serum Cr should be obtained at T= 24 H, 48H, 72H then Q 24H if delayed excreation
For elevated MTX level or delayed excretion monitor serum creatinine q 12-24 hours and MTX level q
24 hours.
Doses of leucovorin > 25 mg PO should be given IV due to saturation of absorption. Leucovorin
contain calcium and should not be given at the rate faster than 160 mg per minute.
During MTX administration maintain urine pH 7-8 at all times.
Mucositis grading system
Severity
Stomatitis
Gastritis
Colitis
Grade I
Painless ulcers, erythema or mild soreness in the
absence of lesion
Grade II
Painful erythema, edema Requiring medical management Abdominal pain with mucus and/or
or ulcers but can eat or or non-surgical treatment
blood in stool
swallow
Grade III
Painful erythema, edema Bleeding without perforation, Abdominal pain, fever, change in
or ulcers requiring IV uncontrolled by outpatient bowel habits with ileus or peritoneal
hydration
medical management, requiring signs and radiographic or biopsy
hospitalization or surgery
documentation
Grade IV
Severe ulceration or Perforation or bleeding requiring Perforation or requiring surgery or
requires parenteral or emergency surgery
toxic megacolon
enteral nutrition support
or prophylactic intubation
121

Excretion
/Toxicity
Expected
excretion
24 H MTX level
48 H MTX level
72 H MTX level
Leucovorin rescue
=< 10 uM
< 1 uM
< 0.1 uM

15 mg/m2 q 6 H PO/IV until MTX level
< 0.1 uM
< 0.1 uM
Recheck MTX level/Cr q 24 H;
discontinue leucovorin when MTX level
< 0.1 uM
< 0.1 uM
Recheck MTX level/ Cr q 24 H;
< 0.1 uM or normalized Cr or resolved
mucositis
15 mg/m2 q 3 H IV until MTX level
< 0.1 uM
mucositis
Grade I
Mild-Delayed
excretion
Grade I
Mild toxicity
Grade II
Moderate toxicity
Grade III
Severe Toxicity
Grade IV
Life threatening
0.1-0.49 uM
11-49 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
11-49 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
50-499 uM
and/or
>100% increase
Cr
1-4.9 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
1-4.9 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
5-99 uM
and/or
>100% increase
Cr
0.5-4.9 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
0.5-4.9 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
5-49 uM
and/or
>100% increase
Cr
>= 500 uM
>= 100 uM
>= 50 uM

< 0.1 uM
mucositis
Nephrology consultation
1,500 mg/m2 q 3 H IV until MTX level
< 0.1 uM
< 0.1 uM
122

Venous access
o Placement of central venous access device is strongly recommended but not required.
Prophylactic antibiotics
o All patient should receive prophylaxis for PCP
First line: Bactrim 5 mg/kg/day PO divided BID (Max: 320 mg TMP/day) given 3
consecutive days per week
Second line: Dapsone 1 mg/kg/day po daily (Max: 100 mg/day)
Splenectomy or splenic irradiation
o All patients undergoing splenectomy or splenic irradiation should be immunized with
polyvalent pneumococcal, HIB and meningococcal (unless received previously). Irradiated
spleen left in situ may not be fully functional. For patients who are to have splenectomy, give
vaccines prior to splenectomy. Ten to fourteen days prior to laparotomy is optimal. Penicillin
prophylaxis also recommended for splenectomized patients.
HSV prophylaxis
o Herpes prophylaxis (such as acyclovir 10 mg/kg BID day 5-15) should be administered for
those with past history of herpestic stomatitis. Patient with mucositis on therapy should have
viral culture performed and treatment started (acyclovir 750 mg/m 2/day IV) if herpes is
documented.
General guidelines
o The uses of antiemetic and/or analgesics are allowable and encouraged as appropriate
during therapy. Additional corticosteroid should be avoided as an antiemetic or premedication.
123

Months
0
3
6
9
12
15
18
21
24
30
36
42
48
54
60
72
84
96
108
120
PE
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Lab
X
X
X
X
X
CXR
CT/PET
X
ECHO/EKG
Pul Fx
Sex/Bone
X
Renal
X
X
X
T4/TSH
X
Breast
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PE: physical exam to include BP, growth, Tanner staging (for all patient > 10 y/o) and closely exam
irradiated areas for sign of skin and secondary cancer.
Lab: CBC and ESR every visit. ALT/AST, BUN, Cr, Bilirubin and ferritin at 12 months post chemo, then
annually for 5 years.
CXR: chest x-ray
CT/PET: off therapy CT or PET scan should be limited to the original site of disease involvement for
Stage I and II, CT neck/chest/abdomen/pelvis should be done for Stage III and IV.
ECHO/EKG: LV function evaluation by ECHO or MUGA with EKG.
Sex/Bone: Begin sex hormone monitoring once patient is greater than 12 y/o including LH, FSH,
Estradiol/Testosterone. Bone density should be done at the end of therapy then 5 and 10 years off
therapy.
Renal: for patient who received cisplatin or abdominopelvic radiation only. Checks UA, BUN, Cr if
abnormal obtain Cr clearance.
T4/TSH: serum T4 and TSH level at 0 and 6 months off therapy, then yearly for patient receiving
mantel or cervical XRT.
Breast: begin semiannual breast exam at puberty and instruct in monthly self-exam.
Lymphoma: Off therapy follow up guideline
124

Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301]
Protocol name:
Thai-POG HOD 1301
Protocol for:
Low Risk Hodgkin Disease
Low Risk Hodgkins Disease:
Reference: COG AHOD 0431

Total Pages: 6
o Stage I-A Hodgkin Lymphoma with no bulk disease.

o Stage II-A Hodgkin Lymphoma with no bulk disease.
Patients name
Hospital
HN
Disease Status:
Stage: (circle one)
Age
kg Ht
BW
Sex
cm BSA
m2
Treatment schema:
I
II
III
IV
Extranodal involvement: (circle one)
Yes
No
Systemic symptoms: (circle one) A
Bulk disease: (circle one)
No
Yes
LR-Induction-I
drugs)
LR-Induction-II
CT/PET/Gal
Primary site:
RER
Pathologic subtype:
SER
LR-Consolidation-I
LR-Consolidation-I
CT/PET/Gal
CT/PET/Gal
Post Induction Evaluation: (circle one)

CR
PR
SD
PD
Post Induction risk group:
RER
Post Consolidation Evaluation: (circle one)

CR
PR
SD PD
IFRT: (circle one) Yes
SER
IFRT
CR
CT/PET/Gal
No
If yes, Total dose
CR
End of therapy
PR, SD
Disease reassessment
Post IFRT evaluation : (circle one)

CR
PR
SD
PD
PD patients will go to salvage protocol at any point of Rx

* Please see definition on next page
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301]
125

Patients name
Hospital
HN
Age
kg Ht
BW
Sex
cm BSA
Phase I: LR-INDUCTION-I (3 weeks)
Date Start:___________
Week
Day
2
8
1
1
10
3
15
m2
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
Investigation:
CBC/diff
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB
ECHO or MUGA and EKG
PFT
Drug
D
B
V
E
Start
Induction-II
on day 22
or when
blood count
parameters
are met.
B*
V
E
+
+
+
+
+
+
Route
+
+
Dosage
Days
Doxorubicin (DOX)
IV push over 5 minutes
25 mg/m2/dose
1, 2
Bleomycin (BLEO)
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
1
8*
Vincristine (VCR)
IV push over 1 minute
1.4 mg/m2/dose
1, 8
Etoposide (ETOP)
IV over 60-120 minutes
125 mg/m2/dose
1, 2, 3
Note
RER = Rapid Early Response, SER = Slow Early Response
Gal: Gallium scan
126

Patients name
Hospital
HN
Age
kg Ht
BW
Phase II: LR-INDUCTION-II (3 weeks)
Sex
cm BSA
m2
Start Induction-II on Day 22 of Induction-I and ANC 750/ul and PLT 75,000/ul whichever occurs later.
Week
Day
1
1
2
8
10
3
15
21
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
Investigation:
D
B
V
E
CBC/diff
CT C/A/P or PET CT
+
+
Drug
Start Next
course
Consolidation-I
on day 22 or
when blood
count
parameters are
met.
D
B*
V
E
+
+
Route
+
+
+
Dosage
Days
Doxorubicin (DOX)
25 mg/m2/dose
1, 2
Bleomycin (BLEO)
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
1
8*
Vincristine (VCR)
1.4 mg/m2/dose
1, 8
Etoposide (ETOP)
125 mg/m2/dose
1, 2, 3
Note
CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Induction-II
Post Induction treatment assignment:
Treatment response
Complete Response
Partial response or Stable disease
Progressive disease
Post induction risk group

RER
SER
Progression
Post Induction regimen

Consolidation-I and II
Consolidation-I and II then IFRT
Salvage protocol
127

Patients name
Hospital
HN
Age
kg Ht
BW
Phase III: LR- CONSOLIDATION -I (3 weeks)
Sex
cm BSA
m2
Start Consolidation-I on Day 22 of Induction-II and ANC 750/ul and PLT 75,000/ul whichever occurs
later.
Week
Day
1
1
2
8
10
3
15
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
Investigation:
D
B
V
E
CBC/diff
PFT
+
+
+
+
Drug
D
B*
V
E
+
+
Route
+
+
Dosage
Start
ConsolidationII on day 22 or
when blood
count
parameters are
met.
Days
Doxorubicin (DOX)
25 mg/m2/dose
1, 2
Bleomycin (BLEO)
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
1
8*
Vincristine (VCR)
1.4 mg/m2/dose
1, 8
Etoposide (ETOP)
125 mg/m2/dose
1, 2, 3
128

Patients name
Hospital
HN
Age
kg Ht
BW
Phase IV: LR- CONSOLIDATION -II (3 weeks)
Sex
cm BSA
m2
Start Consolidation-II on Day 22 of Consolidation-I and ANC 750/l and PLT 75,000/l whichever
occurs later.
Week
Day
1
1
2
8
3
15
10
21
4
22
Date due
Date given
Proceed to
next phase of
therapy (IFRT
or End of
therapy)
according to
End of
Induction
disease
status
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
Investigation:
CBC/diff
ESR, ELyte, BUN, Cr, AST, ALT,
TB,DB
CT C/A/P or PET CT
Drug
D
B
V
E
D
B*
V
E
+
+
+
+
Route
+
+
+
Dosage
Days
Doxorubicin (DOX)
25 mg/m2/dose
1, 2
Bleomycin (BLEO)
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
1
8*
Vincristine (VCR)
1.4 mg/m2/dose
1, 8
Etoposide (ETOP)
125 mg/m2/dose
1, 2, 3
Note
End of Consolidation treatment
End of Induction disease
response
Status
RER
Complete response
SER
Partial response, Stable disease
SER
Progression
Any
Post Consolidation management
End of therapy evaluation

IFRT
IFRT
Salvage protocol
129

Patients name
Hospital
HN
BW
Age
kg Ht
Sex
cm BSA
m2
Phase V: INVOLVED FIELD RADIATION THERAPY (IFRT): For SER patient only
Date Start:____
Radiation field
:(
:(
Number of fractions
:(
Date start
:(
:(
CT date
:(
Note
IFRT should be done within 6 weeks after start consolidation-II with ANC > 1,000/l and
Platelets > 100,000/ l
CT chest abdomen and pelvis should be done 6-8 weeks after complete radiation
Post IFRT treatment assignment:

Post radiation treatment response
Complete response
Progression
Post IFRTmanagement
End of therapy evaluation
Disease reassessment: repeat biopsy or PET scan to
evaluate residual disease
Salvage protocol
130

Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302]
Protocol name: Thai-POG HOD 1302
Reference:
COG AHOD0831, St. Judes MIED
Protocol for: Intermediate Risk/High Risk Hodgkin Disease Total Pages: 8
Intermediate Risk Hodgkin Disease:
High Risk Hodgkin Disease:
o Stage I-E, I-B and I-A Hodgkin Lymphoma
o Stage III-B Hodgkin Lymphoma.
with bulk disease.
o Stage IV-B Hodgkin Lymphoma.
o Stage II-E-, II-B and II-A Hodgkin
Lymphoma with bulk disease.
o Stage III-A Hodgkin Lymphoma.
o Stage IV-A Hodgkin Lymphoma.
Patients name
Age
Sex
Hospital
HN
BW
kg Ht
BSA
Disease Status:
Treatment schema:
Stage: (circle one)
I
II III
IV
HR-Induction-I drugs)
Extranodal involvement: (circle one) Yes No
HR-Induction-II
Systemic symptoms: (circle one)
A
B
Bulk disease: (circle one)
Yes No
CT/PET/Gal
BMA and Biopsy (only >= II-B):
SER
Site involvement:
RER
Pathologic subtype:
HR-Intensification-I
HR-Consolidation-I
Disease stage:
Risk group:
HR-Intensification-II
HR-Consolidation-II
Post Induction Evaluation:
CR PR SD PD
Post induction risk group: RER SER
CT/PET/Gal
CT/PET/Gal
Post Intensification Evaluation: ***SER only
CR, PR, SD
CR
PR
SD
PD
HR-Consolidation-I
Post Consolidation Evaluation:
HR-Consolidation-II
CR
PR
SD
PD
CR
IFRT Date:
CT/PET/Gal
Total dose
Post IFRT evaluation: (circle one)CR PR SD PD
CR, PR, SD
IFRT
CR, PR, SD
IFRT
* Please see definition on the next page
CT/PET/Gal
CT/PET/Gal
CR
PR, SD
End of therapy
Disease reassessment
PD patients will go to salvage protocol at any point of Rx
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302]
131

Patients name
Hospital
HN
Age
kg Ht
BW
Phase I: HR-INDUCTION-I (3 weeks)

1
1
Week
Day
Sex
cm BSA
m2
2
2
8
10
3
15
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
PRED _____ mg PO BID
CPM _______ mg IV
G-CSF _______ mcg SQ/IV
D
B
V
E
Start
InductionII on day
22 or when
blood
count
parameters
are met.
B*
V
E
Investigation:
CBC/diff
ECHO or MUGA and EKG
PFT
Drug
Doxorubicin (DOX)
Bleomycin (BLEO)
+
+
+
+
Route
Dosage
IV push over 5 minutes 25 mg/m2/dose
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
IV push over 1 minute 1.4 mg/m2/dose
Vincristine (VCR)
IV over 60-120 minutes 125 mg/m2/dose
Etoposide (ETOP)
PO
20 mg/m2/dose BID
Prednisone (PRED)
Cyclophosphamide (CPM) IV over 30-60 minutes 600 mg/m2/dose
SubQ or IV
5 mcg/kg/dose
G-CSF
+
+
+
+
Days
1, 2
1
8*
1, 8
1, 2, 3
1-7
1, 2
Daily begin on day 4
Hold on day 8
Note
Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC
> 1,000/ul post nadir. Do not give on day 8.
Note

RER = Rapid Early Response, SER = Slow Early Response
Gal: Gallium scan
132

Patients name
Hospital
HN
BW
Phase II: HR-INDUCTION-II (3 weeks)
Last day of G-CSF:
Age
Sex
kg Ht
cm BSA
m2
Start Induction-II on Day 22 of Induction-I and ANC 750/ul (at least 2 days after stop G-CSF) and PLT
75,000/ul whichever occurs later.
1
1
Week
Day
2
8
10
3
15
21
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
D
B
V
E
B*
V
Start Next
course
(IntensificationI or
Consolidation-I)
on day 22 or
when blood
count
parameters are
met.

CPM _______ mg IV
Investigation:
CBC/diff
+
+
+
+
CT C/A/P or PET CT
+
+
+
BM aspiration and biopsy
(+)
Drug
Doxorubicin (DOX)
Bleomycin (BLEO)
Route
IV over 10 minutes
Vincristine (VCR)
Etoposide (ETOP)
Prednisone (PRED)
Cyclophosphamide (CPM)
G-CSF

PO
SubQ or IV
Dosage
25 mg/m2/dose
5 Units/m2/dose
10 Units/m2/dose*
1.4 mg/m2/dose
125 mg/m2/dose
20 mg/m2/dose BID
600 mg/m2/dose
5 mcg/kg/dose
Days
1, 2
1
8*
1, 8
1, 2, 3
1-7
1, 2
Hold on day 8
Note
BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement
at diagnosis
Treatment response
Disease Status
Post Induction regimen
RER
Complete Response
Consolidation-I and II
SER
Partial response or Stable
Intensification-I and II then Consolidation-I and II
disease
Progression
Progressive disease
Salvage protocol
133

Patients name
Age
Sex
Hospital
HN
BW
kg Ht
cm BSA
m2
Phase V: HR-CONSOLIDATION-I (3 weeks): RER: start after Induction-II/ SER: start
after Intensification-II
Start Consolidation-Ion Day 22 of Induction-II in RER or Intensification-II in SER and ANC 750/ul (at
least 2 days after stop G-CSF) and PLT 75,000/ul whichever occurs later.
1
1
Week
Day
2
8
10
3
15
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO _______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
D
B
V
E
B*
V
E
Start
ConsolidationII on day 22 or
when blood
count
parameters are
met.

CPM _______ mg IV
Investigation:
CBC/diff
PFT
+
+
+
+
Drug
Doxorubicin (DOX)
Bleomycin (BLEO)
Route
IV over 10 minutes
Vincristine (VCR)
Etoposide (ETOP)
Prednisone (PRED)
Cyclophosphamide (CPM)
G-CSF

PO
SubQ or IV
+
+
Dosage
25 mg/m2/dose
5 Units/m2/dose
10 Units/m2/dose*
1.4 mg/m2/dose
125 mg/m2/dose
20 mg/m2/dose BID
600 mg/m2/dose
5 mcg/kg/dose
+
+
Days
1, 2
1
8*
1, 8
1, 2, 3
1-7
1, 2
Hold on day 8
Note
134

Patients name
Hospital
HN
BW
Phase VI: HR-Consolidation-II (3 weeks) Date Start:
Age
kg Ht
Sex
cm BSA
m2
Last day of G-CSF:
Start Consolidation-II on Day 22 of Consolidation-I and ANC 750/ul (at least 2 days after stop G-CSF)
and PLT 75,000/ul whichever occurs later.
1
1
Week
Day
2
8
10
3
15
21
4
22
Date due
Date given
Medication:
DOX _______ mg IV
BLEO ______/______ mg IV
VCR _______ mg IV
ETOP _______ mg IV
CPM _______ mg IV
D
B
V
E
Proceed to
next phase of
therapy
(IFRT or
salvage
protocol)
according to
End of
Consolidation
evaluation
B*
V
E
Investigation:
CBC/diff
+
+
+
+
+
+
+
CT C/A/P or PET CT
Drug
Doxorubicin (DOX)
Bleomycin (BLEO)
Vincristine (VCR)
Etoposide (ETOP)
Prednisone (PRED)
Cyclophosphamide
(CPM)
G-CSF
(+)
Route
Dosage
IV push over 5 minutes 25 mg/m2/dose
IV over 10 minutes
5 Units/m2/dose
10 Units/m2/dose*
IV push over 1 minute 1.4 mg/m2/dose
PO
20 mg/m2/dose BID
SubQ or IV
5 mcg/kg/dose
Days
1, 2
1
8*
1, 8
1, 2, 3
1-7
1, 2
Hold on day 8
Note
Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul
post nadir. Do not give on day 8.
CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Consolidation-II
BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement at diagnosis
Treatment response
Post Consolidation management
Complete Response/ Partial Response/ Stable disease
IFRT
Progressive disease
Salvage protocol
135

Patients name
Hospital
HN
BW
Phase III: HR-INTENSIFICATION-I (3 weeks):
Only for SER: start after Induction-II
Age
kg Ht
Sex
cm BSA
m2
Date Start: __________
Start Intensification-I on Day 22 of Induction-II and ANC 750/ul (at least 2 days after stop G-CSF) and
PLT 75,000/ul whichever occurs later.
1
1
Week
Day
2
8
10
3
15
4
22
Date due
Date given
Medication:
HD-MTX _______ mg IV
LCV _______ mg IV/PO
M
LLLLLLLLLL
LL
E
E
E
ETOP _______ mg IV
IFOS _______ mg IV
MESNA _______ mg IV
DEX _______ mg IV
Start
Intensification-II
on day 22 or
when blood
count
parameters are
met.
SSS SSS SSS

DDD DDD
DDD
Investigation:
CBC/diff
PFT
+
+
+
+
+
+
Drug
High-dose
Methotrexate (HD-MTX)
Leucovorin (LCV)
Etoposide (ETOP)
Ifosfamide (IFOS)
Mesna
Route
IV drip in 4 hours
Dosage
8,000 mg/m2/day
IV/PO
IV over 4 hours
IV
15 mg/m2/dose q 6 hours
200 mg/m2/day
2,000 mg/m2/day
500 mg/m2/dose
Dexamethasone (DEX)
IV
+
+
Days
Day 1
Day 2, 3, 4
Day 2, 3, 4
Day 2, 3, 4
Day 2, 3, 4
At hour 0, 3, 6 of IFOS
2
40mg/m day divided in 3 dose Day 1, 2, 3
q 8 hours
5 mcg/kg/day
Day 4 then daily
SubQ or IV
G-CSF
Note:
post nadir.
136

Patients name
Hospital
HN
Age
kg Ht
BW
Sex
cm BSA
m2
Phase IV: HR-INTENSIFICATION-II (3 weeks) Date Start:__________Last day of G-CSF: _________

Start Consolidation-II on Day 22 of Intensification-I and ANC 750/ul (at least 2 days after stop G-CSF)
and PLT 75,000/ul whichever occurs later.
1
1
Week
Day
2
8
3
15
21
4
22
Date due
Date given
Medication:
HD-MTX _______ mg IV
LCV _______ mg IV/PO
ETOP _______ mg IV
IFOS _______ mg IV
MESNA _______ mg IV
DEX _______ mg IV
M
LLLLLLLLLLL
L
E
Start next phase

(Consolidation-I
or Salvage) on
day 22 or when
blood count
parameters are
met.
SSS SSS SSS

DDD DDD DDD
G
Investigation:
CBC/diff
+
+
+
+
CT C/A/P or PET CT
+
+
+
(+)
Drug
High-dose Methotrexate
(HD-MTX)
Leucovorin (LCV)
Etoposide (ETOP)
Ifosfamide (IFOS)
Mesna
Route
IV drip in 4 hours
Dosage
8,000 mg/m2/day
Days
Day 1
IV/PO
IV over 4 hours
IV
15 mg/m2/dose q 6 hours
200 mg/m2/day
2,000 mg/m2/day
500 mg/m2/dose
Dexamethasone (DEX)
IV
40mg/m2day divided in 3
dose q 8 hours
5 mcg/kg/day
Day 2, 3, 4
Day 2, 3, 4
Day 2, 3, 4
Day 2, 3, 4
At hour 0, 3, 6 of IFOS
Day 1, 2, 3
SubQ or IV
Day 4 then daily
G-CSF
Note:
post nadir.
CT Chest/Abdomen/Pelvis or PET CT should be done between day 15-18 of Intensification-II
BM aspiration and biopsy only in stage IV patient with positive bone marrow involvement at diagnosis
Treatment response
Complete Response/ Partial Response/ Stable disease
Progressive disease
Post Intensification Management

Consolidation I and II
Salvage protocol
137

Patients name
Hospital
HN
BW
Age
kg Ht
Sex
cm BSA
m2
Phase V: INVOLVED FIELD RADIATION THERAPY (IFRT):
For all IR and HR Hodgkin lymphoma patients

Radiation field
:(
:(
Number of fractions
:(
Date start
:(
:(
Note
)
)
)
)
) CT date: (
IFRT should be done within 6 weeks after start consolidation-II with ANC > 1,000/l and
Platelets > 100,000/ l
CT chest abdomen and pelvis should be done 6-8 weeks after complete radiation
Post IFRT treatment assignment:

Post radiation treatment response
Complete response
Progression
Post IFRTmanagement
End off therapy evaluation
Disease reassessment: repeat biopsy or PET scan to evaluate
residual disease
Salvage protocol
138

Data entry form for non-Hodgkin lymphoma
Address...........................................................................................................................................................
..........................................................................Contact person....................................Tel............................
Fathers name........................................................ Age...........yr Occupation.............................
Mothers name........................................................ Age...........yr Occupation.............................
Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) .....................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...................................
History

A. Blood date (//)
CBC ....
BUN Creatinine Na K .. Cl ... HCO3 .
Ca .. P Mg. AST ALT TB ..
DB... ALP. GGT . LDH ..
CSF (//) WBC ...RBC...
Cytospin
positive
negative for malignancy
GFR (//)
calculated / measured) ml/min/1.73m2
Coagulogram (//) aPTT.PT.INR.fibrinogen..
B. Imaging studies
CT neck (//) .....
CT chest (//) .....
CT abdomen/ pelvis (//) ....
Chest X-Ray (//) .........
Bone scan (//) .........
Gallium scan (optional, //) ........
PET scan (optional, //)...........
Bone marrow aspiration (//)..........
BM biopsy (//) .....
D. Others
Audiogram (//)..........
EKG (//)
Echo (//)
Other (//) ..
Lymphoma: Data entry form for non-Hodgkin lymphoma
139

Non-Hodgkin lymphoma (NHL) Murphy stage
Stage I
Stage II
Stage III
Stage IV
A single tumor (extranodal) or single anatomic area (nodal) with the exclusion of
mediastinum or abdomen
A single tumor (extranodal) with regional lymph node involvement
Two or more nodal areas on the same side of the diaphragm
Two single (extranodal) tumors with or without regional LN involvement on the same
side of the diaphragm
A primary GI tract tumor, usually in the ileocecal area, with or without involvement of
associated mesenteric nodes only, grossly completely resected
Two single tumors (extranodal) on the opposite sides of (above and below) the
diaphragm
All primary intrathoracic (mediastinal, pleural, thymic) tumors
All extensive primary intra-abdominal disease, unresectable
All paraspinal or epidural tumors, regardless of other tumor site(s)
Any of the above with initial involvement of CNS or BM (<25% replacement of
marrow elements without circulating blast cells)
Treatment plan for patients with NHL
Lymphoma: Non-Hodgkin lymphoma (NHL) Murphy stage
140

Treatment plan for patiants with mature B-cell lymphoma
Burkitt lymphoma/leukemia
Atypical Burkitt lymphoma
Diffuse large B-cell lymphoma
Mediastinal large B-cell lymphoma
Mature B-cell lymphoma NOS
Risk stratification
Low Risk
Completely resected stage I or completely resected abdominal stage II lesions.
Standard Risk All cases not eligible for low or high risk. (Murphy Stage III and non- CNS Stage IV)
High Risk
Any CNS involvement and/or bone marrow involvement. For CNS involvement one or more
of the following applies:
(1) Any L3 blasts in CSF
(2) Cranial nerve palsy (if not explained by extracranial tumor)
(3) Clinical spinal cord compression
(4) Isolated intracerebral mass
(5) Parameningeal extension: cranial and/or spinal
Treatment plan
Induction X2
Consolidation X2 Continuation
Risk group
Pre-Phase
Low risk
COPAD
Standard risk
COP
CYM
COPAD-M3
High risk
COP
CYVE
Seq. No 1,2,3,4
COPAD-M8
Intrathecal treatment
Age
<1
1-2
2-3
>3
Methotrexate
8 mg
10 mg
12 mg
15 mg
Hydrocortisone
8 mg
10 mg
12 mg
15 mg
Lymphoma: Treatment plan for patiants with mature B-cell lymphoma
Ara-C
16 mg
20 mg
24 mg
30 mg
141

Treatment plan for patients with anaplastic large cell lymphoma
Risk stratification
Low Risk
Standard Risk
Stage I disease completely resected

No skin involvement
No mediastinal involvement
No liver, spleen or lung involvement
High Risk
Includes patients with any of the following features:
Presence of biopsy proven skin lesions (except skin lesions overlying an
involved node or isolated skin disease*)
Presence of mediastinal involvement
Presence of liver (liver enlargement 5 cm and / or nodular liver), spleen
(spleen enlargement and / or nodular spleen) or lung involvement (biopsy is
not necessary for obvious lesions)
*Isolated skin lesions is not considered a high risk factor. ALCL confined to skin is extremely rare in childhood
and may represent a distinct form of the disease. Currently it is not clear whether patients with isolated skin
disease and no extracutaneous manifestations need chemotherapy at all. Such patients should have careful
staging, central pathology review of histology and discussed with the study coordinator before adopting a wait
and see approach.
Treatment plan
Risk group
Low risk
Standard risk
High risk
Pre-Phase
COP
COP
COP
Intrathecal Treatment
Age
<1
1-2
2-3
>3
Intensive phase
A1 B1 A2
A1 B1 A2 B2 A2 B3
AM1 BM1 AM2 BM2 AM2 BM3
Methotrexate
6 mg
8 mg
10 mg
12 mg
Hydrocortisone
4 mg
6 mg
8 mg
10 mg
Lymphoma: Treatment plan for patients with anaplastic large cell lymphoma
Ara-C
16 mg
20 mg
24 mg
30 mg
142

Appendix I: Supportive care guidelines for high dose methotrexate administration
for ThaiPOG-NHL13-BL protocol
1) Hydration
Pre-hydrate with 250 ml/m2/h with alkalinization for a minimum of 2 hours in order to achieve a pH of
> 6.5.
Methotrexate is administered in dextrose (piggyback into IVF with bicarb) at a dose of 3,000 mg/m2
over 3 hours in standard risk and a dose of 8,000 mg/m2 over 4 hours in high risk participants.
After methotrexate infusion, continue hydration at a rate of 3,000 mLs/m2/day with dextrose 5% with
added NaHCO3 (40 mEq/l) and KCL (20 mEq/l) to maintain urinary pH > 7 for a further 48 hours in standard
risk patients (with normal rate of hydration the following 24 hours) or 72 hours after infusion in high risk
patients.
2) Drug interactions
Drugs which compromise renal function (e.g. aminoglycosides) can decrease clearance of
methotrexate and lead to systemic toxicity. Avoid concurrent use of NSAIDs, omeprazole, azole antifungals,
salicylates and sulphonamides. Large doses of penicillin may interfere with the active renal tubular section of
methotrexate.
3) Leucovorin
Leucovorin (folinic acid) 15 mg/m2 should be given orally or IV every 6 hours. The dose should be
rounded up to the nearest 5 mg. The rescue begins 24 hours from the start of the methotrexate infusion.
Intrathecal drugs should be given before rescue starts. If vomiting occurs within 30 minutes, repeat the dose. If
persistent vomiting or diarrhea occurs, give leucovorin by IV injection. Methotrexate levels, urea and
electrolytes should be measured daily for 3 days after methotrexate infusion. Strict attention should be paid to
fluid balance. The leucovorin dose should be modified as required based in the methotrexate level.
Leucovorin dosage adjustments: Patients will have their leucovorin rescue increased if they meet any
of the following criteria:
Dose 3 g/m2
8 g/m
MTX Level
24 hour
> 5 M
> 10 M
48 hour
> 1 M
> 1 M
72 hour
> 0.1 M
>0.1 M
*If the 48 hour MTX level is < 0.15 M /l, discontinue leucovorin rescue.
If the patient meets any of these criteria, the leucovorin dosage will be individualized and plasma
concentrations will be monitored until the plasma level is <0.1 M.
High risk group: Patients who experience Grade IV GI toxicity after COPAD M8 #1 will receive
COPAD M3 for their subsequent courses. Patients who experience Grade IV GI toxicity after COPAM M3 #1
will begin leucovorin at 18 instead of 24 hours with subsequent HDMTXs.
A further check on the MTX level should be done at 120 hours in high risk COPADM8 courses to
ensure that the level does not increase again after IT MTX, and to alter leucovorin rescue as required.
Hydration should continue beyond 72 hours in the following situations:
(1) If there is still evidence of tumor lysis
(2) If cyclophosphamide infusion is still in process
(3) If the MTX level is still >0.15 M.
Lymphoma: Appendix I: Supportive care guidelines for high dose methotrexate administration for
ThaiPOG-NHL13-BL protocol
143

Appendix II: Supportive care guidelines for high dose methotrexate administration
for ThaiPOG-NHL13-ALCL protocol
Methotrexate at 1,000 mg/m2 over 24 hours (course A1, A2, A3, B1, B2 and B3)
1) Hydration
Pre- hydrate with 125 ml/m2/h (dextrose saline with NaHCO3 40 mmol/l) for a minimum of 2 hours in
order to achieve a pH of 7 and a urine output of 100 ml/m2/h.
During and after MTX infusion, continue hydration at a rate of 3,000 ml/m2 with NaHCO3 40 mmol/l
and KCL 20 mmol/l added to dextrose saline to maintain urinary pH 7 for a further 48 hours after the end of
the methotrexate infusion.
Methotrexate levels, urea and electrolytes should be measured daily for at least 3 days after MTX
infusion.
Strict attention should be paid to fluid balance.
2) Methotrexate
Methotrexate 1,000 mg/m2 in 0.9% saline is given on day 1 with 1/10 of the dose as initial IV over 30
minutes and 9/10 of the dose as 23.5 hour infusion
methotrexate.
Prophylactic co-trimoxazole (if given) should be stopped one week prior to MTX administration.
4) Leucovorin
Leucovorin (folinic acid) 15 mg/m2 should be given IV for an optimal rescue at hrs 42, 48 and 54 from
the start of MTX infusion.
MTX plasma concentrations are measured at hrs 24 and hr 48 from start of MTX infusion. The
expected MTX plasma concentrations are as follows.
Time from start of MTX Expected MTX level
Leucovorin dose
< 30 mol/L
24 hrs
42 hrs
15 mg/m2 IV
< 0.25 mol/L
48 hrs
15 mg/m2 IV
54 hrs
15 mg/m2 IV
If the plasma MTX concentration at 48 hrs from start of MTX infusion is <0.25 mol/L then leucovorin
rescue is stopped after 54 hrs and no more measurements of the plasma MTX concentrations are needed.
If the plasma MTX concentration at 48 hrs from the start of MTX is >0.25 mol/L, continue the
leucovorin rescue beyond 54 hrs according the schedule below, and continue with measurement of the plasma
MTX concentration every 24 hrs.
Lymphoma: Appendix II: Supportive care guidelines for high dose methotrexate administration for
ThaiPOG-NHL13-ALCL protocol
144

MTX level at 48 hrs or later from start of MTX infusion*
Leucovorin rescue
(mol/L)
(mg/m2 IV q6h)
0.25 1
15
1-2
30
2-3
45
3-4
60
4-5
75
>5
**
* MTX level to be measured every 24 hrs until the level falls below 0.25 mol/L, then discontinue leucovorin
** mg leucovorin IV q6h = MTX level (mol/L) x body weight (kg)
Methotrexate at 3,000mg/m2 over 3 hours (course AM1, AM2, AM3, BM1, BM2 and BM3)
1) Hydration
Pre-hydrate with 125 ml/m2/h (dextrose saline with NaHCO3 40 mmol/l) for a minimum of 2 hours in
order to achieve a pH of 7 and a urine output of 100 ml/m2/h.
During and after MTX infusion, continue hydration at a rate of 3,000 ml/ m2 with NaHCO3 40 mmol/l
and KCL 20 mmol/l added to dextrose saline to maintain urinary pH 7 for a further 48 hours.
Methotrexate levels, urea and electrolytes should be measured daily for 3 days after MTX infusion.
Strict attention should be paid to fluid balance
2) Methotrexate
Methotrexate is administered in saline at a dose of 3,000 mg/m2 over 3 hours.
methotrexate.
Prophylactic co-trimoxazole (if given) should be stopped one week prior to MTX administration.
4) Leucovorin
Leucovorin (folinic acid) 15 mg/m2 should be given orally or iv every 6 hours. The dose should be
rounded up to the nearest 5 mg. If leucovorin is given orally, other oral drugs should be avoided within 30
minutes of leucovorin administration. If vomiting occurs within 30 minutes, repeat the dose. If persistent
vomiting or diarrhoea occurs, then give leucovorin by IV injection.
Methotrexate levels, urea and electrolytes should be measured daily for 3 days after methotrexate
infusion.
Leucovorin doses should be modified according to the MTX level. The level should be measured
every 24 hours until rescue is complete i.e. plasma MTX level < 0.15 mol/L.
145

The rescue begins 24 hours from the start of MTX infusion and stops when the MTX level is
< 0.15 mol/L. This may be achieved with fewer than 12 doses. In this situation stop leucovorin after this
time.
If the MTX level does not fall as expected, increase leucovorin as shown below.
Time from
start of MTX
48 hrs
72 hrs
96 hrs
120 hrs
<0.15
None
None
None
None
0.15-2
15 mg/m2 IV q6h
15 mg/m2 IV q6h
15 mg/m2 IV q6h
15 mg/m2 IV q6h
MTX level (mol/L)

2-20
20-100
2
15 mg/m IV q6h 10 mg/m2 IV q3h
10 mg/m2 IV q3h 100 mg/m2 IV q3h
>100
100 mg/m2 IV q3h
1,000 mg/m2 IV q3h
1,000 mg/m2 IV q3h
1,000 mg/m2 IV q3h
146

Evaluation for matual B cell lymphoma
Tests
Pretreatment
COP
Induction
CBC
Chemistries
PT/PTT, INR,
fibrinogen, ESR
UA
Surgical Bx of lesion
To do prior to each course of therapy

BMA/Bx
CSF
Imaging study
(eg. CT neck, chest,
abdomen, pelvis)
Bone scan
Gallium scan / PET
(optional)
EKG/Echo
to do prior to each course of therapy

See CR Eval See CR Eval
(LR)
(SR and HR)
See CR Eval See CR Eval
(LR)
(SR and HR)
To do with all IT treatmenrts
CT on D7 of See CR Eval See CR Eval
COP
(LR)
(SR and HR)
To follow up as indicated
Consolidation Maintenance
Prior to each course of Doxorubicin if clinically

indicated
End of
therapy
CR Evaluation: Includes BM exam (not required if BM negative at diagnosis), surgical biopsy of lesion (if
having residual tumor) and imaging studies of primary tumor sites. The time of evaluation varies with risk
group:
- Low risk (LR) after completion of COPAD#2
- Standard risk (SR) after completion of CYM#1
- High risk (HR) after completion of CYVE#2
Lymphoma: Evaluation for matual B cell lymphoma
147

Evaluation for Anaplastic Large Cell Lymphoma
Tests
Pre-treatment Pre-phase
CBC
Chemistries
PT/PTT, INR, fibrinogen,
ESR
UA
Surgical Bx of lesion
BMA/Bx
CSF
Imaging study
(eg. CT neck, chest,
abdomen, pelvis)
Bone scan
Gallium scan / PET
(optional)
EKG/Echo
Intensive phase
End of therapy
To do with all IT treatmenrts

After the 3rd course in intensive
phase
Prior to each course of Doxorubicin if clinically

indicated
Lymphoma: Evaluation for Anaplastic Large Cell Lymphoma
148

Treatment protocol for low risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-LR]
Protocol name ThaiPOG-NHL-13-BL-LR
Protocol for Mature B-cell Lymphoma Low Risk
Reference:
SJBC3 Protocol
Open Date
January 2014
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Inclusion Criterla
Days
Prednisolone
Vincristine
Cyclophosphamide
Doxorubicin
G-CSF
Given dose/day
.mg
.mg
.mg
.mg
..mcg
Low Risk Group

COPAD Course 1
Completlely stage I
1
Completely resected abdominal stage II lesion

3
Drug
Vincristine
Prednisolone
Dosage
2 mg/m2 (max single dose 2 mg) IV bolus on Day 1 and 6
60 mg/m2/day (divided into bid doses) orally on Days 1-7
inclusive.
Cyclophosphamide 250 mg/m2/dose every 12 hours as a 15 minute infusion on
Days 1-3 inclusive (500 mg/m2/day). The first dose should be
given on day 1 prior to the start of the doxorubicin infusion.
Hydration should be maintained at a rate of 3,000 mL/m2/day
(125 mL/m2/hr). Continue hydration until 12 hours after the last
dose of cyclophosphamide. Total daily mesna dose to be
equal to 60-100% of the daily cyclophosphamide dose
Doxorubicin
60 mg/m2 as a 6 hour infusion, after the first dose of
cyclophosphamide on Day 1
G-CSF
5 mcg/kg/day subcutaneously on Day 7-21 inclusive. G-CSF
should be discontinued when the post nadir ANC reaches
2,000/mm3, even if prior to day 21.
Date
Remarks
COPAD Course 2
Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide dose
Lymphoma: Treatment protocol for low risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 149
LR]

Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-SR]
Protocol name ThaiPOG-NHL-13-BL-SR
Protocol for Mature B-cell Lymphoma Standard Risk
Reference:
SJBC3 protocol
Open Date
January 2014
Standard Risk: Treatment Plan (COP COPADM3(x2) CYM(x2))
Standard Risk: Pre-phase: COP
Days
1
2
Cyclophosphamide
Vincristine
Prednisolone
IT MTX

IT HC

IT Ara-C
Given dose/day
.mg
.mg
.mg
Drug
Cyclophosphamide
Vincristine
Prednisolone
IT medications
Dosage
300 mg/m2 as an infusion over 15 minutes on Day 1
1 mg/m2 (max single dose 2 mg) IV bolus on Day 1
See Intrathecal Treatment for dosing (If blasts identified on this
LP, patients will be moved to high risk group)
Tumor response evaluation should be performed on day 7 before proceeding with COPADM3 course1
Non-responding patients (<20% reduction in size) will be treated with high risk group protocol (start with
COPADM8 course1)
Standard Risk Group Pre-phase
COP
Date
Remarks
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 150
BL-SR]

Standard Risk : Induction (COPADM3 x 2 courses)
The first COPADM3 course starts on Day 8 as long as clinical condition permits. Please note that COPADM3
course 1 and 2 are identical.
Days
Vincristine
Prednisolone
Methotrexate
Leucovorin
Cyclophosphamide
Doxorubicin
IT MTX
IT HC
G-CSF
Rituximab
Given dose/day
.mg
.mg
.mg
...mg/dose
.mg
.mg
.mg
..mcg
.mg
Drug
Vincristine
Prednisolone
Methotrexate
Leucovorin
Dosage
2 mg/m2 (max dose 2 mg) as IV bolus on Day 1
60 mg/m2/day (divided into bid doses) orally on Days 1-7 inclusive
3,000 mg/m2 in dextrose 5% as IV infusion over 3 hours on Day 1.
15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as
required depending on methotrexate levels. This begins at 24
hours from the start of the methotrexate infusion.
Cyclophosphamide 250 mg/m2/dose every 12 hours (500 mg/m2/day) as an infusion
over 15 minutes on days 2-4 ( 6 doses). The first dose is given
before start of the doxorubicin infusion. Continue hydration at a
rate of 3,000 mls/m2/day until 12 hours after the last dose of
cyclophosphamide. Total daily mesna dose to be equal to 60100% of the daily cyclophosphamide dose
Doxorubicin
cyclophosphamide.
IT MTX
Methotrexate and hydrocortisone IT injection on Days 2 and 6 (See
Intrathecal Treatment for dosing). Administer Day 2 IT 12-24 hours
after HDMTX starts and before leucovorin rescue begins
G-CSF
5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. GCSF should be discontinued when the post nadir ANC reaches
2,000/mm3 even if prior to Day 21.
Rituximab
375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers
of hepatitis B should be closely monitored for clinical and
laboratory signs of active HBV infection and for signs of
hepatitis.
BL-SR]

Course #2 of COPADM3 should start when ANC 1.0 x 109/L and platelets 100,000 x 109/L. However, the
course should not be given less than 14-21 days after the start of COPADM3 #1 and should be delayed for 24
hours from the last dose of G-CSF.
COPADM3 Course 1
Date
Remarks
COPADM3 Course 2
BL-SR]

Standard Risk: Consolidation (CYM x 2 courses)
Each cycle of CYM should start when ANC 1.0 x 109/L and platelets 100,000 x 109/L. Please note that
CYM course 1 and 2 are identical.
Days
Methotrexate
Leucovorin
Cytarabine
IT MTX
IT-Ara-C
IT HC
G-CSF
Rituximab
Given dose/day
.mg
...mg/dose
.mg
..mcg
.mg
Drug
Dosage
Methotrexate 3,000 mg/m2 in dextrose 5% as IV infusion over 3 hours on Day 1.
Leucovorin
required depending on methotrexate levels. This begins at 24 hours from
the start of the methotrexate infusion
Cytarabine
100 mg/m2 in either dextrose or saline as continuous infusion over 24
hours. Repeat daily from Day 2-6 inclusive (total of 5 days).
IT
Methotrexate and hydrocortisone IT injection on Day 2. Cytarabine and
medications hydrocortisone IT injection on Day 7 (See Intrathecal Treatment for
dosing). Administer Day 2 IT methotrexate and hydrocortisone 12-24
hours after HDMTX starts and before leucovorin begins.
G-CSF
5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF
should be discontinued when the post nadir ANC reaches 2,000/mm3,
even if prior to Day 21.
Rituximab
375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of
hepatitis B should be closely monitored for clinical and laboratory
signs of active HBV infection and for signs of hepatitis.
-Following recovery from CYM #1, a full assessment of response should be performed. Any residual masses
should be surgically excised, or biopsied if excision is not possible.
If histology negative Continue with CYM #2
If histology positive (even if completely resected) Change to high risk protocol by starting with CYVE
#1
BL-SR]

Standard Risk Group - Consolidation
CYM Course 1
Date
Remarks
CYM Course 2
BL-SR]

Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL-HR]
Protocol name ThaiPOG-NHL-13-BL-HR
Protocol for Mature B-cell Lymphoma High Risk
Reference:
SJBC3 protocol
Open Date
January 2014
Inclusion criteria
Bone marrow involvement
CNS involvement
Any L3 blasts in CSF
Clinical spinal cord compression
Isolated intracerebral mass
Parameningeal extension: cranial and/or spinal
Cranial nerve palsy (if not explained by extracranial tumor)
High Risk : Treatment Plan ( COP COPADM8(x2) CYVE(x2) Maintenance 1,2,3,4 )
High Risk : Pre-phase: COP
Days
1
2
Cyclophosphamide
Vincristine
Prednisolone

IT MTX

IT HC
IT Ara-C
Leucovorin
Given dose/day
.mg
.mg
.mg
Drug
Cyclophosphamide
Vincristine
Prednisolone
IT medications
...mg/dose
Leucovorin
High Risk Group Pre-phase
Dosage
Methotrexate, cytarabine, and hydrocortisone IT injection on
Days 1, 3, and 5 (See Intrathecal Treatment for dosing)
5 mg/m2/dose (max 5 mg) po given at 24 and 30 hours after IT
on Days 2 & 4
Date
Remarks
COP
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 155
HR]

High Risk : Induction (COPADM8 course 1)
COPADM8 course 1 should start on day 8 of COP pre-phase therapy, as long as clinical condition permits.
Please note that COPADM8 course 1 and 2 are different.
Days
1
2
3
4
5
6
7
Vincristine

Prednisolone
Methotrexate

Leucovorin
Cyclophosphamide
Doxorubicin

IT MTX

IT HC

IT-Ara-C
G-CSF

Rituximab

Given dose/day
.mg
.mg
Drug
Vincristine
Prednisolone
Dosage
inclusive
8,000 mg/m2 in dextrose 5% as IV infusion over 4 hours on Day 1
.mg Methotrexate
...mg/dose Leucovorin
required depending on methotrexate levels. This begins at 24
hours from the start of the methotrexate infusion.
2
2
.mg Cyclophosphamide 250 mg/m /dose every 12 hours (500 mg/m /day) as an infusion
over 15 minutes on days 2-4 ( 6 doses). The first dose is given
before start of the doxorubicin infusion. Continue hydration until
12 hours after the last dose of cyclophosphamide. Total daily
mesna dose to be equal to 60-100% of the daily
cyclophosphamide dose
.mg Doxorubicin
cyclophosphamide.
Methotrexate, cytarabine, and hydrocortisone IT injection on Days
IT medications
2, 4, and 6 (See Intrathecal Treatment for dosing). Administer
Day 2 IT 12 & 24 hours after HDMTX startsb and before
leucovorin rescue begins.
5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive.
..mcg G-CSF
G-CSF should be discontinued when the post nadir ANC reaches
2,000/mm3 even if prior to Day 21.
375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma)
.mg Rituximab
Carriers of hepatitis B should be closely monitored for clinical
and laboratory signs of active HBV infection and for signs of
hepatitis.
HR]

High Risk Group - Induction
COPADM8 Course 1
Date
Remarks
HR]

High Risk : Induction (COPADM8 course 2)
OPADM8 course 2 should start when ANC 1.0 x 109/L and platelets 100,000 x 109/L. The course should
not be given less than 14-21 days after the start of COPADM8 course 1 and should be delayed for 24 hours
from the last dose of G-CSF. Please note that cyclophosphamide dose in COPADM8 course 2 is higher than
the dose in COPADM8 course 1.
Days
1
2
3
4
5
6
7
Vincristine

Prednisolone
Methotrexate

Leucovorin

Cyclophosphamide
Doxorubicin

IT MTX

IT HC

IT-Ara-C
G-CSF

Rituximab

Given dose/day Drug
Dosage
.mg Vincristine
.mg Prednisolone
inclusive
.mg Methotrexate
8,000 mg/m2 in dextrose 5% as IV infusion over 4 hours on
Day 1 (Note: Higher dose than for standard risk group)
15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or
as required depending on methotrexate levels. This begins at
24 hours from the start of the methotrexate infusion.
.mg Cyclophosphamide 500 mg/m2/dose every 12 hours (1,000 mg/m2/day) as an
infusion over 15 minutes on days 2-4 (6 doses). The first dose
is given before start of the doxorubicin infusion. Continue
hydration until 12 hours after the last dose of
cyclophosphamide. Total daily mesna dose to be equal to
60-100% of the daily cyclophosphamide dose
.mg Doxorubicin
cyclophosphamide.
IT medications
Methotrexate, cytarabine, and hydrocortisone IT injection on
Days 2, 4, and 6 (See Intrathecal Treatment for dosing).
Administer Day 2 IT 12 & 24 hours after HDMTX startsb and
before leucovorin rescue begins.
..mcg G-CSF
5 mcg/kg/day by subcutaneous injection on Days 7-21
inclusive. G-CSF should be discontinued when the post nadir
ANC reaches 2,000/mm3 even if prior to Day 21.
.mg Rituximab
375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma)
Carriers of hepatitis B should be closely monitored for
clinical and laboratory signs of active HBV infection and for
signs of hepatitis.
HR]

High Risk Group - Induction
COPADM8 Course 2
Date
Remarks
HR]

High Risk : Consolidation (CYVE x 2 courses)
The first of these two courses should start after COPADM8 cycle 2 when ANC 1.0 x 109/L and platelets
100,000 x 109/L. G-CSF should have been stopped for 24 hours before the start of this course. Please note
that CYVE course 1 and 2 are identical.
Variations in the start/stop times of the agents below are acceptable, as long as the sequence of
administration of the agents and duration of infusions are as close as possible.
Days
1
2
3
4
5
6
7
Cytarabine (continuous) Runs from 20:00-08:00
HD Ara-C

Runs from 08:00-11:00
Etoposide

Runs from 14:00-16.00
GCSF
Rituximab

Given dose/day Drug
Dosage
.mg Cytarabine
50 mg/m2 by continuous infusion over 12 hours. This should start at
(continuous) 20:00 hours and run until 08:00 the following day. Repeat daily x 5.
.mg HD Ara-C
3,000 mg/m2 as IV infusion over 3 hours, to start at the end of the 12
hour infusion of cytarabine for 4 doses (from 08:00 to 11:00 hours).
.mg Etoposide
200 mg/m2 in saline as IV infusion over 2 hours daily x 4 doses.
Etoposide starts at 14:00 hours, 3 hours after end of high dose
cytarabine.
...mcg GCSF
5 mcg/kg/day by subcutaneous injection on Days 7-21 inclusive. G-CSF
should be discontinued when the post nadir ANC reaches 2,000/mm3,
even if prior to Day 21.
.mg Rituximab
375 mg/m2 given on Day 1 (only on CD20+ B-lymphoma) Carriers of
hepatitis B should be closely monitored for clinical and laboratory
signs of active HBV infection and for signs of hepatitis.
CYVE #2: This course is the same as CYVE #1 and starts once ANC 1.0 x 109/L and platelets 100,000 x
109/L (usually by day 25-28).
Following recovery from CYVE #2, a complete response evaluation should be performed. Residual masses
should be surgically excised, or biopsied if excision is not possible.
o If histology negative Continue on protocol
o If histology positive Autologous hematopoietic stem cell transplantation is recommended after
salvage therapy
High Risk Group - Consolidation
Date
Remarks
CYVE Course 1
CYVE Course 2
HR]

High Risk : Maintenance
Maintenance therapy includes 4 sequences/blocks of chemotherapy. Each sequence will begin when ANC
1.0 x 109/L and platelets 100,000 x 109/L.
High Risk : Maintenance (Sequence No. 1)
Days
1
2
3
4
5
6
7

Vincristine
Prednisolone

Cyclophosphamide

Methotrexate
Leucovorin

Doxorubicin
IT MTX
IT HC
IT Ara-C

G-CSF
Given dose/day
.mg
.mg
.mg
.mg
...mg/dose
.mg
...mcg
Drug
Vincristine
Prednisolone
Cyclophospha
mide
Dosage
500 mg/m2/day given daily as IV infusion over 30 minutes on Days 2 and 3.
First dose is given before doxorubicin. Total daily mesna dose to be equal
to 60-100% of the daily cyclophosphamide dose
Methotrexate 8,000 mg/m2 in dextrose 5% IV infusion over 4 hours on Day 1.
Leucovorin
15 mg/m2 orally or IV every 6 hours for a total of 12 doses (or as modified
depending on methotrexate levels). This begins 24 hours from the start of
the methotrexate infusion.
Doxorubicin
60 mg/m2 as a 6 hour infusion, after first dose of cyclophosphamide
IT medications Methotrexate, cytarabine, and hydrocortisone IT injection on Day 2 (See
Intrathecal Treatment for dosing). Administer Day 2 IT 12-24 hours after
HDMTX starts and before leucovorin rescue begins.
GCSF
5 mcg/kg/day by subcutaneous injection starting 24 hours aftercompletion of
chemotherapy. G-CSF should be discontinued when the post nadir ANC
reaches 2,000/mm3
High Risk Group - Maintenance

Maintenance: Sequence No. 1
Date
Remarks
HR]

Days
1
2
Cytarabine
Etoposide
G-CSF
IT MTX

IT HC

IT Ara-C
Given dose/day
.mg
.mg
...mcg
Drug
Cytarabine
Dosage
50 mg/m2/dose as subcutaneous injection every 12 hrs (100 mg/m2/day)
Days 1-5
Etoposide
150 mg/m2 IV infusion over 90 minutes Days 1-3
G-CSF
5 mcg/kg/day by subcutaneous injection starting 24 hours after
completion of chemotherapy. G-CSF should be discontinued when the
post nadir ANC reaches 2,000/mm3.
IT medications For CNS positive only. Given on day1. (See Intrathecal Treatment for
dosing)

Date
Remarks
HR]

Days
1
2
3

Vincristine
Prednisolone
Cyclophosphamide

Doxorubicin
G-CSF

IT MTX

IT HC

IT Ara-C
Given dose/day
.mg
.mg
.mg
Drug
Vincristine
Prednisolone
Cyclophosphamide
.mg Doxorubicin
.mcg GCSF
IT medications

Dosage
500 mg/m2/day given daily as IV infusion over 30 minutes on Days 1
and 2. First dose is given before doxorubicin. Maintain hydration at
3,000 mL/m2/day until 12 hours after 2nd dose. Total daily mesna
dose to be equal to 60-100% of the daily cyclophosphamide dose
60 mg/m2 as a 6 hour infusion, after first dose of cyclophosphamide
5 mcg/kg/day by subcutaneous injection starting 24 hours
aftercompletion of chemotherapy. G-CSF should be discontinued
when the post nadir ANC reaches 2,000/mm3
For CNS positive only. Given on day1. (See Intrathecal Treatment
for dosing
Date
Remarks
HR]

High Risk: Maintenance (Sequence No. 4)
Days
1
2
Cytarabine
Etoposide
G-CSF
IT MTX

IT HC

IT Ara-C
Given dose/day
.mg
.mg
...mcg
Drug
Cytarabine
Dosage
50 mg/m2/dose as subcutaneous injection every 12 hrs (100 mg/m2/day)
Days 1-5
Etoposide
150 mg/m2 IV infusion over 90 minutes Days 1-3
G-CSF
5 mcg/kg/day by subcutaneous injection starting 24 hours after
completion of chemotherapy. G-CSF should be discontinued when the
post nadir ANC reaches 2,000/mm3.
IT medications For CNS positive only. Given on day1. (See Intrathecal Treatment for
dosing)

Date
Remarks
HR]

Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL-LR]
Protocol name ThaiPOG- NHL-13-ALCL-LR
Protocol for Anaplastic Large Cell Lymphoma Low Risk
Reference:
AIEOP ALCL99
Open Date
January 2014
Inclusion criteria
Stage I disease completely resected
Low Risk Group Treatment Plan (P A1 B1 A2 )
Low Risk: Pre-phase (COP)
Days
1
2
Cyclophosphamide
Vincristine
Prednisolone

IT MTX

IT HC
IT Ara-C
Given dose/day
.mg
.mg
.mg
Drug
Cyclophosphamide
Vincristine
Prednisolone
IT medications
Low Risk Group Pre-phase
Dosage
See Intrathecal Treatment for dosing
Date
Remarks
COP
Lymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 165
LR]

Low Risk: Intensive phase (A1 B1 A2)
Low Risk: Intensive phase course A (A1 and A2)
The course of A1 begins at day 6 of Pre-phase treatment. Subsequent course, A2, starts as soon as the
peripheral counts have recovered with when ANC 0.5 x 109/L and platelets 50,000 x 109/L and rising and
patient is clinically well and free of fever for more than 3 days. Please note that course A1 and A2 are
identical.
Days
Dexamethasone
Methotrexate
IT-MHC
Ifosfamide
Mesna
Cytarabine
Etoposide
Given dose/day
.mg
.mg
Drug
Dexamethasone
Methotrexate
Dosage
10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV.
1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30
minutes then 90% as a 23.5h infusion).
..mg/dose Leucovorin
15 mg/m2 IV 42, 48 and 54 hours after the beginning of MTX
infusion.
IT medications
Day 1 (2 - 4 hours after the beginning of Methotrexate infusion)
See Intrathecal Treatment for dosing.
.mg Ifosfamide
800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before
the start of MTX infusion. IV or oral hydration at a rate of 3,000
mls/m2/day should continue until 12 hours after the last dose of
Ifosfamide.
.mg Mesna
Given as an IV bolus 330 mg/m2/dose at 0, 4 and 8 hours after
Ifosfamide.
.mg Cytarabine
150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5.
(300 mg/m2/day)
.mg Etoposide
100 mg/m2 in 2 hour infusion day 4 and 5 (after the infusion of
Cytarabine).
Note: Prophylactic GCSF is not recommended
LR]

Low Risk: Intensive phase course B (B1)
The course of B1 starts as soon as the peripheral counts have recovered with ANC 0.5 x 109/L and
platelets 50,000 x 109/L and rising and patient is clinically well and free of fever more than 3 days.
Days
1
2
3
4
5
Dexamethasone
Methotrexate

IT-MHC

Cyclophosphamide

Doxorubicin

Given dose/day
.mg
.mg
Drug
Dexamethasone
Methotrexate
Dosage
minutes then 90% as a 23.5h infusion).
infusion.
IT medications
Day 1 (2 - 4 hours after the beginning of Methotrexate
infusion) See Intrathecal Treatment for dosing.
.mg Cyclophosphamide 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give
before the start of MTX infusion. Hydration IV or PO at a rate
of 3,000 mls/m2/day should then continue until 12 hours after
the last dose of Cyclophosphamide
.mg Doxorubicin
25 mg/m2 in 1 hour infusion day 4 and 5.
Low Risk Group Intensive phase
Course A1
Date
Remarks
Course B1
Course A2
LR]

Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma
[ThaiPOG- NHL-13-ALCL-SR]
Protocol name ThaiPOG- NHL-13-ALCL-SR
Protocol for Anaplastic Large Cell Lymphoma Standard Risk
Reference:
AIEOP ALCL99
Open Date
January 2014
Standard Risk Group Treatment Plan (P A1 B1 A2 B2 A3 B3 )
Standard Risk : Pre-phase (COP)
Days
Cyclophosphamide
Vincristine
Prednisolone
IT-MHC
Given dose/day
.mg
.mg
.mg
Drug
Cyclophosphamide
Vincristine
Prednisolone
IT medications

COP
Dosage
Date
Remarks
Lymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 168
NHL-13-ALCL-SR]

Standard Risk : Intensive phase (A1 B1 A2 B2 A3 B3)
Standard Risk : Intensive phase course A (A1, A2 and A3)
The course of A1 begins at day 6 of Pre-phase treatment. Subsequent courses, A2 and A3, start as soon as
the peripheral counts have recovered with when ANC 0.5 x 109/L and platelets 50,000 x 109/L and rising
and patient is clinically well and free of fever more than 3 days. Please note that course A1, A2 and A3 are
identical.
Days
Dexamethasone
Methotrexate
IT-MHC
Ifosfamide
Mesna
Cytarabine
Etoposide
Given dose/day Drug

Dosage
mg Dexamethasone 10 mg/m2 (divided into BD doses) from days 1 to 5 orally or IV.
mg Methotrexate
1,000 mg/m2 over 24 hours day 1 (10% of the dose in 30 minutes
then 90% as a 23.5 h infusion)
infusion.
IT medications Day 1 (2 - 4 hours after the beginning of Methotrexate infusion) See
Intrathecal Treatment for dosing.
mg Ifosfamide
800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before the
start of MTX infusion. IV or oral hydration at a rate of 3,000
Ifosfamide.
mg Mesna
Ifosfamide.
mg Cytarabine
150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5. (300
mg/m2/day).
mg Etoposide
Cytarabine).
NHL-13-ALCL-SR]

Standard Risk : Intensive phase course B (B1, B2 and B3)
The courses of B1, B2 and B3 start as soon as the peripheral counts have recovered with ANC 0.5 x 109/L
and platelets 50,000 x 109/L and rising and patient is clinically well and free of fever for more than 3 days.
Please note that course B1, B2 and B3 are identical.
Days
1
2
3
4
5
Dexamethasone
Methotrexate

IT-MHC

Cyclophosphamide

Doxorubicin

Given dose/day
Drug
.mg Dexamethasone
.mg Methotrexate
Dosage
minutes then 90% as a 23.5 h infusion)
infusion.
IT medications
Day 1 (2 - 4 hours after the beginning of Methotrexate infusion)
See Intrathecal Treatment for dosing.
.mg Cyclophosphamide 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give
the last dose of Cyclophosphamide.
.mg Doxorubicin
Standard Risk Group Intensive phase
Course A1
Course B1
Course A2
Course B2
Course A3
Course B3
Date
Remarks
NHL-13-ALCL-SR]

Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma
[ThaiPOG- NHL-13-ALCL-HR]
Protocol name ThaiPOG- NHL-13-ALCL-HR
Protocol for Anaplastic Large Cell Lymphoma High Risk
Reference:
AIEOP ALCL99
Open Date
January 2014
Inclusion criteria
Biopsy proven skin lesions (except skin lesions overlying an involved node or isolated skin disease)
Presence of mediastinal involvement
Presence of liver, spleen or lung involvement (biopsy is not necessary for obvious lesions)
High Risk Group Treatment Plan (P AM1 BM1 AM2 BM2 AM3 BM3)
High Risk: Pre-phase (COP)
Days
1
2
Cyclophosphamide
Vincristine
Prednisolone

IT MHC
Given dose/day
.mg
.mg
.mg
Drug
Cyclophosphamide
Vincristine
Prednisolone
IT medications
High Risk Group Pre-phase
Dosage
Date
Remarks
COP
Lymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 171
13-ALCL-HR]

High Risk: Intensive phase (AM1 BM1 AM2BM2 AM3 BM3)
High Risk: Intensive phase course AM (AM1, AM2 and AM3)
The course of AM1 begins at day 6 of Pre-phase treatment. Subsequent courses, AM2 and AM3, start as
soon as the peripheral counts have recovered with when ANC 0.5 x 109/L and platelets 50,000 x 109/L
and rising and patient is clinically well and free of fever for more than 3 days. Please note that course AM1,
AM2 and AM3 are identical.
Days
Dexamethasone
Methotrexate
Ifosfamide
Mesna
Cytarabine
Etoposide
Given dose/day
.mg
.mg
...mg/dose
Drug
Dexamethasone
Methotrexate
Leucovorin
Dosage
3,000 mg/m2 over 3 hours day 1
as required depending on Methotrexate levels. This begins 24
hours after start of MTX infusion.
.mg Ifosfamide
800 mg/m2 in 1 hour infusion days 1 to 5. On day 1 give before
the start of MTX infusion. IV or oral hydration at a rate of 3,000
Ifosfamide.
.mg Mesna
Ifosfamide.
.mg Cytarabine
150 mg/m2 in 1 hour infusion every 12 hours on day 4 and 5.
(300 mg/m2/day)
.mg Etoposide
Cytarabine).
13-ALCL-HR]

High Risk: Intensive phase course BM (BM1, BM2 and BM3)
The courses of BM1, BM2 and BM3 start as soon as the peripheral counts have recovered with ANC 0.5 x
109/L and platelets 50,000 x 109/L and rising and patient is clinically well and free of fever for more than 3
days. Please note that course BM1, BM2 and BM3 are identical.
Days
1
2
3
4
5
Dexamethasone

Methotrexate

Cyclophosphamide

Doxorubicin
Given dose/day
.mg
.mg
...mg/dose
.mg
.mg
Drug
Dexamethasone
Methotrexate
Leucovorin
Dosage
3,000 mg/m2 over 3 hours day 1
as required depending on Methotrexate levels. This begins 24
hours after start of MTX infusion.
Cyclophosphamide 200 mg/m2 as 60 minute infusion days 1 to 5. On day 1 give
the last dose of Cyclophosphamide
Doxorubicin

High Risk Group Intensive phase
Course AM1
Course BM1
Course AM2
Course BM2
Course AM3
Course BM3
Date
Remarks
13-ALCL-HR]

CNS Germ Cell Tumor

Data entry form
Address...........................................................................................................................................................
Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) .....................................2
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m

() .................................
History
Pre- treatment investigations

Tumor marker (Blood) date (//)
-hCG (serum) ....
AFP(serum)....
Imaging study
MRI primary lesion (//) ......
MRI whole spine (//) .....
*MRI spine should be studied prior to surgery or two weeks after surgery
Cerebrospinal fluid study (//)

CSF study from ventriculostomy
VP shunt
CSF cytology positive
negative
lumbar puncture
*CSF study should be performed two weeks after surgery
-hCG (CSF) ....
AFP(CSF) ....
Primary site (location)
Primary tumor size.
Metastasis site
M 1 CSF +
M 2 brain metastasis by MRI
M 3 spinal cord metastasis by MRI
M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)
Other
Other (//) ...
Initial surgery (//) surgeon........
Operation biopsy partial removal total removal wide excision Other..
Histology ...
Tumor Histology Classification
Teratoma
Immature teratoma
Germinoma
Non-germinoma Yolk sac tumor (Endodermal sinus tumor) Embryonal cell carcinoma
Choriocarcinoma
Mixed germ cell tumor
CNS Germ Cell Tumor: Data entry form
174

Treatment protocol for CNS germinoma [ThaiPOG-BT-13-GCT]
Protocol name ThaiPOG-BT-13-GCT
Protocol for CNS Germinoma (Non-secreting tumor)
Open Date
January 2014
Patient eligibility
CNS germinomatous germinoma
CNS germinoma with syncytiotrophoblast
Exclusion criteria
serum or CSF AFP > 10 ng/dl
serum or CSF -hCG > 50 U/
Patients name.................................................................... Sex................... HN...........................................

Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
Cycle
Agent (s)
Dose (s)
Carboplatin
560 mg/m2 IV drip in 1 hour once daily Day 1
1, 2, 3
Etoposide
150 mg/m2 IV drip in 30 min once daily Day 1-3
*start chemotherapy when ANC > 1,000 mcL and platelet > 100,000/mcL
*Each course of chemotherapy should be started every 21-28 days apart
Cycle
Date
BSA
Carboplatin
Etoposide
1
2
3
Radiation _______________________________________________________________________________
Irradiation should be started after chemotherapy completion for 28 days.
1) Whole ventricle irradiation with a dose of 24 Gy (1.8 2 Gy/ fraction) must be applied with a primary
tumor boost up to 30 Gy or 36-40 Gy (1.8 2 Gy/ fraction) if the tumor response is less than partial
response. For the case that basal ganglia is involved, whole brain irradiation or wider than ventricular
field 24 Gy (1.8 2 Gy/ fraction) should be considered.
2) In case of germinoma with syncytiotrophoblast (serum and CSF AFP < 10 ng/dL and serum or CSF
-hCG positive with the level < 50 U/L), a primary tumor boost up to 50 Gy (1.8 2 Gy/ fraction)
must be considered.
3) In case of M+, craniospinal irradiation (CSI) 24 Gy (1.8 2 Gy/ fraction) must be applied.
4) Intermediate risk disease (elevated -hCG, extensive or multifocal in brain, mixed type), a primary
tumor boost up to 50 Gy (1.8-2 Gy/ fraction) must be considered.
Evaluation and follow up
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
LP (//) ..
LP (//) ..
CNS Germ Cell Tumor: Treatment protocol for CNS germinoma [ThaiPOG-BT-13-GCT]
175

Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT]
Protocol name ThaiPOG-BT-13-NGCT
Protocol for CNS non-germinoma
Open Date
January 2014
Patient eligibility
1. CNS non-germinoma with biopsy proven
Immature teratoma with malignant transformation Yolk sac tumor (endodermal sinus tumor)
Embryonal cell carcinoma
Choriocarcinoma
Mixed germ cell tumor
2. Secreting tumor
serum /CSF AFP > 10 ng/dl OR serum/CSF -hCG > 50 U/L

Cycle
1,2,3
Agent (s)
Ifosfamide
Mesna
Carboplatin
Etoposide
Carboplatin
Etoposide
4,5,6,7,8
Dose (s) 2
1,800 mg/m
IV drip in 1-2 hour daily Day 1-3
400 mg/m2 prior to ifosfamide infusion and then at 3,6,9,12 hr
after ifosfamide
infusion
560 mg/m2 IV drip in 1 hour Day 1
150 mg/m22 IV drip in 2 hour daily Day 1-3
560 mg/m2 IV drip in 1 hour Day 1
150 mg/m IV drip in 2 hour daily Day 1-3
*start chemotherapy when ANC > 1,000 /mcL and platelet > 100,000 mcL
*Each course of chemotherapy should be started every 21-28 days apart
Cycle
1
Date
BSA
Ifosafmide
Carboplatin
Etoposide
2
3
Irradiation
4
5
6
7
8
* Second look surgery may be considered before irradiation.
*Irradiation should be started after chemotherapy completion for 28 days.
1) Whole ventricle irradiation with a dose of 24 Gy (1.8 2 Gy/ fraction) must be applied with a primary
tumor boost up to 50 Gy (1.8 2 Gy/ fraction). For the case that basal ganglia is involved, whole
brain irradiation 24 Gy or wider than ventricular field 24 Gy (1.8 2 Gy/ fraction) should be
considered.
2) In case of M+, craniospinal irradiation (CSI) 30 Gy (1.8 2 Gy/ fraction) must be applied with a boost
up dose to 40 Gy (1.8 2 Gy/ fraction) for gross residual disease.
CNS Germ Cell Tumor: Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT]
176

MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
LP (//) ..
LP (//) ..
CNS Germ Cell Tumor: Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT]
177

Medulloblastoma
Data entry form
Address...........................................................................................................................................................
Date of Birth (dd/mm/yy)......................................... Date of Diagnosis (dd/mm/yy) .....................................2
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m

() .................................
Histology
Embryonal CNS tumors
Medulloblastoma/supratentorial PNET
Atypical/rhabdoid teratoid tumor
Pineloblastoma
Ependymoblastoma
History
Imaging study
MRI primary lesion (//) .....
*MRI spine should be studied prior to surgery or two weeks after surgery

CSF study from
ventriculostomy
VP shunt
CSF cytology
positive
negative
lumbar puncture
*CSF study should be performed two weeks after surgery.

Primary tumor size.
Metastasis site
M 1 CSF +
Initial surgery (//)
Histology (medulloblastoma only)
Subtype
Classical
Desmoplastic Anaplastic/Large cell
Risk group
Average risk (Gross total removal AND M0)
High risk (Less than gross total removal AND/OR M+)
Less than gross total removal (residual tumor > 1.5 cm2 by MRI)
M 1 CSF +
M 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)
Other (//) ...
CNS Germ Cell Tumor: Medulloblastoma
178

Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR]
Protocol name ThaiPOG-BT-13-MB-AVR
Protocol for Average risk medulloblastoma
Open Date
January 2014
Irradiation guideline, CSI (24 Gy with a boost up to 54.6 Gy to the posterior fossa is needed to be applied
within 28 days after surgical removal.
Chemotherapy during irradiation (Irradiation started within 28 days after surgical removal)
Vincristine
1.5 mg/m2 weekly x 6 weeks
Week
1
2
3
4
5
6
Vincristine (Actual dose)
Date
CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 179

Chemotherapy after irradiation (started within 28 days after irradiation completion)
Cycle
Agent (s)
Dose (s)
1,3,5,7,9
Cyclophosphamide 800 mg/m2 IV drip 1 hour once daily Day 1-3
Vincristine
1.5 mg/m2 IV push once daily Day 1,8,15
Carboplatin
200 mg/m2 IV drip in 1 hour once daily Day 1-3
2,4,6,8,10
Etoposide
*New cycle of chemotherapy should be started within 21-28 days
*chemotherapy should be started when ANC > 1,000 /mcL and platelet > 100,000 /mcL
*G-CSF should be started at 24-36 hr after completion of each course of chemotherapy
Cycle
Date
BSA
Cyclophosphamide
Vincristine
Carboplatin
Etoposide
1
2
3
4
5
6
7
8
9
10
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
LP (//) ..
LP (//) ..
CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 180

Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR]
Protocol name ThaiPOG-BT-13-MB-HR
Protocol for High risk medulloblastoma
Open Date
January 2014
In case of non-complete remission, secondary surgery may be needed to be applied after irradiation.
Irradiation guideline, CSI (36 Gy with a boost up to 54.6 Gy to the posterior fossa is needed to be applied
within 28 days after surgical removal.
Chemotherapy during irradiation (Irradiation started within 28 days after surgical removal)
Vincristine
1.5 mg/m2 weekly x 6 weeks
Week
1
2
3
4
5
6
Vincristine (Actual dose)
Date
CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR]
181

Chemotherapy after irradiation (started within 28 days after irradiation completion)
Cycle
Agent (s)
Dose (s)
1,3,5,7,9
Cyclophosphamide 800 mg/m2 IV drip 1 hour once daily Day 1-3
Vincristine
1.5 mg/m2 IV push once daily Day 1,8,15
Carboplatin
2,4,6,8,10
Etoposide
*New cycle of chemotherapy should be started within 21-28 days
*chemotherapy should be started when ANC > 1,000 /mcL and platelet > 100,000 /mcL
*G-CSF should be started at 24-36 hr after completion of each course of chemotherapy
Cycle
Date
BSA
Cyclophosphamide
Vincristine
Carboplatin
Etoposide
1
2
3
4
5
6
7
8
9
10
In case of non-complete remission, secondary surgery is needed to be applied.
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
LP (//) ..
LP (//) ..
CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR]
182

Infant Brain Tumors (Age < 3 years old)

Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() .................................
Histology
History

Imaging study
MRI primary lesion (//) .....
MRI spine should be studied prior to surgery or two weeks after surgery
CSF study from
ventriculostomy
VP shunt
lumbar puncture
CSF cytology
positive
negative
CSF study should be performed two weeks after surgery.
Primary tumor size.
Metastasis site
M 1 CSF +
Initial surgery (//)
Histology
Embryonal CNS tumors
Medulloblastoma
Supratentorial PNET Pineloblastoma
Atypical/rhabdoid teratoid tumor
Ependymoblastoma
Ependymoma
High grade gliomas
Choroid plexus carcinoma
Risk group
Average risk (Gross total removal AND M0)
High risk (Less than gross total removal AND/OR M+) 2
Less than gross total removal (residual tumor > 1.5 cm by MRI)
M 1 CSF +
M 3 spinal cord metastasis by MRI M 4 Extra CNS metastasis (bone, bone marrow, liver, lung)
Other (//) ...
Infant Brain Tumors (Age < 3 years old): Data entry form
183

Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB]
Protocol name
Protocol for
Reference
Open Date
ThaiPOG-BT-13-IFB
Infant Brain Tumors (Age < 3 year old)
Rutkowski S et al N Engl J Med 2005;352:978-86.
January 2014

Age (yy/mm/dd).............................. BW..........................kg Ht..............................cm BSA.........................m2
Cycle
Week 1,10,19,28,37,46
Agent (s)
Cyclophosphamide
Vincristine
Dose (s)
800 mg/m2 IV drip 1 hour once daily Day 1-3
1.5 mg/m2 IV push once daily Day 1
HDMTX
5 gm/m2 IV drip in 4 hours Day 1
Vincristine
HDMTX
5 gm/m2 IV drip in 4 hours Day 1
Vincristine
Carboplatin
Etoposide

Week 3,12,21,30,39,48
Week 5,14,23,32,41,50
Week 7,16,25,34,43,52
*start chemotherapy when ANC > 750/mcL and platelet > 80,000 mcL
Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 184

Week
Date
BSA Cyclophosphamide Vincristine HDMTX
Carboplatin Etoposide
1
3
5
7
10
12
14
16
19
21
23
25
28
30
32
34
37
39
41
43
46
48
50
52
The protocol will be finished at 1 year or the patient reaches 3 years of age, whatever comes first.

MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
MRI (//) ..
LP (//) ..
LP (//) ..

Irradiation guideline
*Start radiation after finished chemotherapy*
1. For embryonal CNS tumors and choroid plexus carcinoma
*Dose of radiation depends on the patients age on the day of starting radiation*
-If age above 12 months but less than 18 months,
M0; posterior fossa or tumor bed 54-60 Gy
M+; CSI 12 Gy with boost at posterior fossa or tumor bed 54-60 Gy
M0; CSI 12 Gy with boost at posterior fossa or tumor bed 54-60 Gy
-If age above 36 months,
2. For ependymoma
-Focal irradiation 54-60 Gy
3. For high grade gliomas
-Focal irradiation 54-60 Gy
Infant Brain Tumors (Age < 3 years old): Irradiation guideline
187

High dose methotrexate infusion guideline
HD MTX administration
Hold bactrim, NSAID, penicillins, PPI or aspirin containing medication on the day of IV MTX infusion
and for at least 72 hours after start MTX infusion.
Hours -6 to 0: D5W+40-60 mEq NaHCO3/L+ 10 mEq KCL/L at 200 ml/m2/H to achieve urine pH 7-8
Hours 0 to 4: Methotrexate 5 g/m2 in 500 ml/m2 D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125
ml/m2/h IV over 4 hours. All doses should be round up to the next highest full gram value.
Hours 4 to 54: Post-hydration with D5W +40 mEq NaHCO3/L+ 10 mEq KCL/L at 125 ml/m2/h.
Hour 24: Begin leucovorin 15 mg/m2 PO/IV Q 6 hours. Beginning at T=24h (from the beginning of
MTX infusion) and continue until serum MTX is < 0.1 uM or until delayed excretion criteria is reached.
Laboratory monitoring
MTX level and serum Cr should be obtained at T= 24 H, 48H, 72H then Q 24H if delayed excreation
For elevated MTX level or delayed excretion monitor serum creatinine q 12-24 hours and MTX level q
24 hours.
Doses of leucovorin > 25 mg PO should be given IV due to saturation of absorption. Leucovorin
contain calcium and should not be given at the rate faster than 160 mg per minute.
During MTX administration maintain urine pH 7-8 at all times.
Mucositis grading system
Severity
Stomatitis
Gastritis
Colitis
Grade I
Painless ulcers, erythema or mild soreness in the
absence of lesion
Grade II
Painful erythema, edema Requiring medical management Abdominal pain with mucus and/or
or ulcers but can eat or or non-surgical treatment
blood in stool
swallow
Grade III
Painful erythema, edema Bleeding without perforation, Abdominal pain, fever, change in
or ulcers requiring IV uncontrolled by outpatient bowel habits with ileus or peritoneal
hydration
medical management, requiring signs and radiographic or biopsy
hospitalization or surgery
documentation
Grade IV
Severe ulceration or Perforation or bleeding requiring Perforation or requiring surgery or
requires parenteral or emergency surgery
toxic megacolon
enteral nutrition support
or prophylactic intubation
Infant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline
188

Excretion
/Toxicity
Expected
excretion
24 H MTX level
48 H MTX level
72 H MTX level
Leucovorin rescue
=< 10 uM
< 1 uM
< 0.1 uM

< 0.1 uM
< 0.1 uM
Recheck MTX level/Cr q 24 H;
< 0.1 uM
15 mg/m2 q 6 H PO/IV until MTX level <
0.1 uM
mucositis
15 mg/m2 q 3 H IV until MTX level < 0.1
uM
mucositis
Grade I
Mild-Delayed
excretion
Grade I
Mild toxicity
Grade II
Moderate toxicity
Grade III
Severe Toxicity
Grade IV
Life threatening
0.1-0.49 uM
11-49 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
11-49 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
50-499 uM
and/or
>100% increase
Cr
1-4.9 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
1-4.9 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
5-99 uM
and/or
>100% increase
Cr
0.5-4.9 uM
and/or
25-50% increase
Cr
and/or
Grade I-II
stomatitis
0.5-4.9 uM
and/or
50-100% increase
Cr
and/or
On previous or
current course of
HD MTX: Grade
III-IV stomatitis,
myelosupression
5-49 uM
and/or
>100% increase
Cr
>= 500 uM
>= 100 uM
>= 50 uM

< 0.1 uM
mucositis
1,500 mg/m2 q 3 H IV until MTX level <
0.1 uM
< 0.1 uM
Infant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline
189

Neuroblastoma
International neuroblastoma risk group (INRG) staging system
Stage
L1
L2
M
MS
Description
Localized tumor not involving vital structures as defined by the list of image-defined risk factors and
confined to one body compartment
Locoregional tumor with presence of one or more image-defined risk factors
Distant metastatic disease (except stage MS)
Metastatic disease in children younger than 18 months with metastases confined to skin. Liver,
and/or bone marrow
Image-Defined Risk Factors in Neuroblastic Tumors

Ipsilateral tumor extension within two body compartments
- Neck-chest, chest-abdomen, abdomen-pelvis
Neck
- Tumor encasing carotid and/or vertebral artery and/or internal jugular vein
- Tumor extending to base of skull
- Tumor compressing the trachea
Cervico-thoracic junction
- Tumor encasing brachial plexus roots
- Tumor encasing subclavian vessels and/or vertebral and/or carotid artery
- Tumor compressing the trachea
Thorax
- Tumor encasing the aorta and/or major branches
- Tumor compressing the trachea and/or principal bronchi
- Lower mediastinal tumor, infiltrating the costo-vertebral junction between T9 and T12
Thoraco-abdominal
- Tumor encasing the aorta and/or vena cava
Abdomen/pelvis
- Tumor infiltrating the porta hepatis and/or the hepatoduodenal ligament
- Tumor encasing branches of the superior mesenteric artery at the mesenteric root
- Tumor encasing the origin of the coeliac axis, and/or of the superior mesenteric artery
- Tumor invading one or both renal pedicles
- Tumor encasing the aorta and/or vena cava
- Tumor encasing the iliac vessels
- Pelvic tumor crossing the sciatic notch
Intraspinal tumor extension whatever the location provided that:
- More than one third of the spinal canal in the axial plane is invaded and/or the perimedullary
leptomeningeal spaces are not visible and/or the spinal cord signal is abnormal
Infiltration of adjacent organs/structures
- Pericardium, diaphragm, kidney, liver, duodeno-pancreatic block, and mesentery
Conditions to be recorded, but not considered imaged-defined risk factors
- Multifocal primary tumors
- Pleural effusion, with or without malignant cells
- Ascites, with or without malignant cells
Neuroblastoma: International neuroblastoma risk group (INRG) staging system
190

Pre-treatment risk classification modified by ThaiPOG
INRG
Stage
Age
(months)
L1/L2
Any
L1
Any
<18
L2
18
Any
Tumor histology
GN maturing
GNB intermixed
Any, except GN
maturing or
GNB intermixed
Any, except GN
maturing or
GNB intermixed
GNB nodular;
Neuroblastoma
Any
Tumor differentiation
MYCN
Shimada
histology
Pre-treatment
risk group
Any
Any
Any
Very low
Any
Any
Differentiating
Poorly differentiated
or undifferentiated
Any
Non-Amp
Amp
Non-Amp
Non-Amp
Amp
Non-Amp
Amp
Any
Any
Very low
High
Favorable
Low
Unfavorable
Intermediate
Favorable
Unfavorable
Low
Intermediate
Any
Intermediate
High
Intermediate
<18
M
Any
Any
Any
High
High
18
Favorable
Very low
Non-Amp
MS
<18
Any
Any
Unfavorable
High
Amp
Any
High
Abbreviation: GN= Ganglioneuroma; GNB= Ganglioneuroblastoma; Non-Amp = MYCN non-amplified;
Amp=MYCN amplified.
Neuroblastoma: Pre-treatment risk classification modified by ThaiPOG
191

Schematic treatment
Protocol for very low/ low risk neuroblastoma
(ThaiPOG-NB-13-LR)
Very Low/ Low risk Neuroblastoma*
Stage MS
Non-stage MS
No complication
Respiratory compromise
Severe liver dysfunction
Close observe
Chemotherapy (low-risk
protocol)
150 cGy 2-3 times to the
anterior 2/3 of the liver through
lateral oblique ports
Surgical removal of 1st tumor
>50% resection
<50% resection
Close observe
Chemotherapy
(low-risk protocol)
*Gangioneuroma maturing and Gangliomeuroblastoma intermixed complete resection and observation

Chemotherapy doses are adjusted for children < 365 days of age or who are 12 kg in weight and are
given as mg/kg.
Cycle
1
2
3
4
Days
1
2
3
22
43 44 45
64 65 66
Carboplatin
Etoposide
Cyclophosphamide
Doxorubicin
Drug
Carboplatin
Etoposide
Cyclophosphamide
Doxorubicin
Dosage
560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4
120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4
1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3
30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle 2,4
Note: After each cycle administer G-CSF 5 mcg/kg SQ starting 24- 36 hours after last dose of
chemotherapy. Continue until the absolute neutrophil count (ANC) is > 1,000/mm 3 for two consecutive
days following the nadir for myelosuppression.
Start chemotherapy when ANC > 1,000/mm3, platelets > 75,000/mm3.
Hold doxorubicin if bilirubin > 3.0 mg/dl. Hold doxorubicin if ECHO SF <29%
Neuroblastoma: Schematic treatment
192

Protocol for standard risk neuroblastoma
(ThaiPOG-NB-13-SR)
Chemotherapy doses are adjusted for children < 365 days of age or who are 12 kg in weight and are
given as mg/kg.
Cycle
Days
Carboplatin
Etoposide
Cyclophosphamide
Doxorubicin
1
2
2
22
Assess treatment response, and perform surgery if feasible

Cycle
5
6
Days
85
86
87
106
Carboplatin
Etoposide
Cyclophosphamide
Doxorubicin
43
3
44
45
64
4
65
66
127
7
128
129
8
148
Assess treatment response, and perform surgery if residual primary tumor detected
Drug
Dosage
Carboplatin
560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4,6,7
Etoposide
120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4,5,7
Cyclophosphamide 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3,5,6,8
Doxorubicin
30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle 2,4,6,8
Note: After each cycle administer G-CSF 5 mcg/kg SQ starting 24- 36 hours after last dose of
chemotherapy. Continue until the absolute neutrophil count (ANC) is > 1,000/mm3 for two
consecutive days following the nadir for myelosuppression.
Start chemotherapy when ANC > 1,000/mm3, platelets > 75,000/mm3.
Hold doxorubicin if bilirubin > 3.0 mg/dl. Hold doxorubicin if ECHO SF < 29%.
After four cycles, assess treatment response, and perform surgery if feasible.
After eight cycles, assess treatment response, and perform surgery if residual primary tumor
detected.
At the end of 4 cycles and again post-cycle #8: CT or MRI of primary site, bone scan, MIBG scan (if
positive at diagnosis) and bone marrow aspirates and biopsies.
193

Protocol for high risk neuroblastoma
(ThaiPOG-NB-13-HR)
Induction Chemotherapy
Induction
Agent (s)
Cycle 1,2
Topotecan
Cyclophosphamide
Cycle 3,5
Cisplatin
Etoposide
Cycle 4,6
Cyclophoshamide
Doxorubicin
Vincristine
Dose (s)
1.2 mg/m2 IV on daily Day 1-5
>12 kg 400 mg/m2 IV once daily Day 1-5
12 kg 13.3 mg/kg IV once daily Day 1-5
>12 kg 2,100 mg/m2 IV once daily Day 1,2
12 kg 70 mg/kg IV once daily Day 1,2
>12 kg & 12 mo 0.67 mg/m2 IV once daily Day 1-3
12 kg & 12 mo 0.022 mg/kg IV once daily Day 1-3
<12 mo 0.017 mg/kg IV once daily Day 1-3
Subsequent cycle begin 21 days after the previous cycle when the ANC > 1,000 /mm3 and platelets > 75,000/L, following nadir.
194

Recommended MIBG treatment
HD-MIBG in HSCT patients
Aim to eradicate tumor cells
18 mCi/kg in single visit
- Since only 150-200 mCi/week can be obtained, the plan is to give weekly dose until
achieving the goal
- eg. 30 kg patient needs 18 x 30 = 540 mCi to give weekly dose x 3 weeks
LD-MIBG in non-HSCT patients
Maintenance low dose (30 mCi) given every 3 months and to continue during maintenance therapy
until the completion of 13 Cis-retinoic acid except for the duration of local XRT (LD-MIBG should be
held during the local XRT treatment)
To give as outpatient setting with 2-3 hours of observation post MIBG
Neuroblastoma: Recommended MIBG treatment
195

Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...................................
History

A. Blood date (//)
CBC ....
BUN Creatinine Na K .. Cl ... HCO3 .
Ca .. P . Mg. AST ALT .
TB .. DB... ALP. GGT
LDH .. Serum NSE .. Urine VMA .
GFR (//)
calculated / measured) ml/min/1.73m2
B. Imaging studies
CT Neck (//) .....
CT chest (//) .....
CT abdomen/ pelvis (//) ....
Chest X-Ray (//) .........
Bone scan (//) .........
MIBG scan (//) .....
Bone marrow aspiration/biopsy (//) 1.positive 1.1 minimal 1.2 extensive
2. negative
Bone marrow result.........
D. Others
Audiogram (//)..........
EKG (//)
Echo (//)
Other (//) ...
Neuroblastoma: Data entry form
196

Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR]
Protocol name ThaiPOG- NB-13-LR
Protocol for Low Risk Neuroblastoma
Reference
Adapted from Baker DL, et al., N Engl J Med. 2010 Sep 30;363(14):1313-23
Open Date
January 2014
Given dose/day
.....................mg
.....................mg
.....................mg
.....................mg
Drug
Carboplatin
Etoposide
Cyclophosphamide*
Doxorubicin
Dosage
560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle 1,2,4
120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle 1,3,4
1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle 2,3
30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of cycle
2,4
.....................mg Mesna*
200 mg/m2 (or 6.5 mg/kg) IV immediately before and then every
3 hours x 4 doses post cyclophosphamide (total 5 doses)
...................mcg GCSF
5 mcg/kg/day SC starting 24 hours after completion of each
cycle of chemotherapy and continue until ANC > 1,000/mm3 x 2
days
Cycle
1
2
3
4
Days
1
2
3
22
43 44 45
64 65 66
Carboplatin
Etoposide
Cyclophosphamide*
Doxorubicin
Cycle Cycle day

Treatment
Date given
Remarks
1
Carboplatin/ Etoposide
NSE/VMA
1
2
Etoposide
3
Etoposide
2
1
Carboplatin/Cyclophos*/ Doxorubicin
NSE/VMA
1
Cyclophos*/Etoposide
NSE/VMA
3
2
Etoposide
3
Etoposide
1
Carboplatin/Etoposide/Doxorubicin
NSE/VMA
4
2
Etoposide
3
Etoposide
3
3
Requirements to begin chemotherapy: ANC > 1,000/mm and platelet count > 75,000/mm
* Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide dose
Post-treatment evaluations
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination, if initial BM involvement (//)......
.
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR]
197

Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR]
Protocol name ThaiPOG- NB-13-SR
Protocol for Standard Risk Neuroblastoma
Reference
Adapted from Baker DL, et al., N Engl J Med. 2010 Sep 30;363(14):1313-23
Open Date
January 2014
Given dose/day
Drug
Dosage
..........................mg Carboplatin
560 mg/m2 or 18 mg/kg IV over 1 hour on Day 1 of cycle
1,2,4,6,7
..........................mg Etoposide
120 mg/m2 or 4 mg/kg IV over 2 hours on Day 1-3 of cycle
1,3,4,5,7
..........................mg Cyclophosphamide* 1,000 mg/m2 or 33 mg/kg over 1 hour on Days 1 of cycle
2,3,5,6,8
..........................mg Doxorubicin
30 mg/m2 or 1 mg/kg IV over 15-60 minutes on Day 1 of
cycle 2,4,6,8
..........................mg Mesna*
200 mg/m2 (or 6.5mg/kg) IV immediately before and then
every 3 hours x 4 doses post cyclophosphamide (total 5
doses)
........................mcg GCSF
5 mcg/kg/day SC starting 24 hours after completion of each
cycle of chemotherapy and continue until ANC > 1,000/mm3
x 2 days
Cycle
Days
Carboplatin
Etoposide
Cyclophosphamide*
Doxorubicin
1
2
2
22
43
3
44
45
64
4
65
66
Cycle Cycle day

Treatment
Date given
Remarks
1
Carboplatin/ Etoposide
NSE/VMA
1
2
Etoposide
3
Etoposide
2
1
NSE/VMA
1
Cyclophos*/Etoposide
NSE/VMA
3
2
Etoposide
3
Etoposide
1
Carboplatin/Etoposide/Doxorubicin
NSE/VMA
4
2
Etoposide
3
Etoposide
Requirements to begin chemotherapy: ANC > 1,000/mm3 and platelet count > 75,000/mm3
Neuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR]
198

Assess treatment response, and perform surgery if feasible
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Cycle
5
6
7
8
Days
85
86
87
106
127 128 129
148
Carboplatin
Etoposide
Cyclophosphamide*
Doxorubicin
Cycle Cycle day
Treatment
Date given
Remarks
1
Cyclophos*/ Etoposide
NSE/VMA
5
2
Etoposide
3
Etoposide
6
1
NSE/VMA
1
Carboplatin/Etoposide
NSE/VMA
7
2
Etoposide
3
Etoposide
8
1
Cyclophos*/ Doxorubicin
NSE/VMA
3
Requirements to begin chemotherapy: ANC > 1,000/mm and platelet count > 75,000/mm3
Assess treatment response, and perform surgery if residual primary tumor detected
CT /MRI (//) .....
Bone scan (//) .........
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR]
199

Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR]
Protocol name ThaiPOG- NB-13-HR
Protocol for High Risk Neuroblastoma
Open Date
January 2014
Induction I
Given dose/day
Drug
..........................mg Topotecan
..........................mg Cyclophosphamide
Dosage
1.2 mg/m2 IV once daily Day 1-5
5 mcg/kg/day SC starting 24 hours after completion of
each cycle of chemotherapy and continue until ANC
> 1,000/mm3 x 2 days
........................mcg GCSF*
Cycle
Days
Topotecan
Cyclophosphamide
1
3
2*
3
Cycle Cycle day

Treatment
Date given
1
Cyclophosphamide/ Topotecan
NSE/VMA
2
Cyclophosphamide / Topotecan
1
3
4
5
1
NSE/VMA
2
2*
3
4
5
*To give GCSF at 10 mcg/kg/day after cycle 2 if plan to collect stem cells (frozen)
Remarks
Requirements to begin chemotherapy

ANC > 1,000/mm3 and platelet count > 75,000/mm3
Serum creatinine < 1.5 mg/dL, bilirubin < 1.2 mg/dL.
Urinalysis < 25 RBC/hpf and Specific Gravity 1.010
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR]
200

Induction II
Given dose/day
...................................mg
Drug
Cisplatin
...................................mg
Etoposide
...................................mg
Cyclophoshamide**
...................................mg
Doxorubicin
...................................mg
Vincristine
...................................mg
Mesna**
Dosage
>12 kg 2,100 mg/m2 IV once daily Day 1-2
12 kg 70 mg/kg IV once daily Day 1-2
>12 kg & 12 mo 0.67 mg/m2 IV once daily Day 1-3
12 kg & 12 mo 0.022 mg/kg IV once daily Day 1-3
< 12 mo 0.017 mg/kg IV once daily Day 1-3
420 mg/m2 (or 14 mg/kg) IV immediately before and then
every 3 hours x 4 doses post cyclophosphamide (total 5
doses)
5 mcg/kg/day SC starting 24 hours after completion of
each cycle of chemotherapy and continue until ANC >
1,000/mm3 x 2 days
...................................mcg GCSF*
Cycle
3
Day
1 2 3 4
Cisplatin

Etoposide

Cyclophoshamide
Doxorubicin
Vincristine
4
2 3
2 3 4

6*
2 3
201

Induction II (continue)
Cycle Cycle day
6*
1
2
3
4
1
2
3
1
2
3
4
1
2
3
Treatment
Cisplatin/Etoposide
Cisplatin/Etoposide
Cisplatin/Etoposide
Cisplatin
Cyclophosphamide**/ Doxorubicin/ Vincristine
Doxorubicin/ Vincristine
Cisplatin/Etoposide
Cisplatin/Etoposide
Cisplatin/Etoposide
Cisplatin
Doxorubicin/ Vincristine
Date
given
Remarks
NSE/VMA
NSE/VMA
NSE/VMA
NSE/VMA
* To give GCSF 10 mcg/kg/day after cycle 6 if plan to collect stem cells (fresh) in case of no HD-MIBG
planned
** Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide dose
Evaluation treatment response
CT /MRI (//) .....
Bone scan (//) .........
MIBG (//) ......
NSE/VMA (//)
202

High Risk Neuroblastoma Treatment Plan (ThaiPOG-NB-13-HR) ICE
Given dose/day
Drug
Dosage
........................mg Carboplatin
635 mg/m2 IV Day 1
........................mg Etoposide
100 mg/m2/day IV Day 2, 3, 4
........................mg Ifosfamide
2,000 mg/m2/day IV Day 2, 3, 4
........................mg Mesna
650 mg/m2 IV immediately before and then 3 and 6 hours after
ifosfamide (total 3 doses)
......................mcg GCSF
5 mcg/kg/day SC starting 24 hours after completion of each cycle of
chemotherapy and continue until ANC > 1,000/mm3 x 2 days
Day
Carboplatin
Etoposide
Ifosfamide
Mesna
203

High Risk Neuroblastoma Treatment Plan (ThaiPOG-NB-13-HR) ICE (continue)
Cycle Cycle day
1
2
1
3
4
1
2
2
3
4
3
1
2
3
4
4
1
2
3
4
Treatment
Carboplatin
Ifosfamide /Etoposide
Carboplatin
Carboplatin
Carboplatin
Date given
Remarks
NSE/VMA
NSE/VMA
NSE/VMA
NSE/VMA

CT /MRI (//) .....
Bone scan (//) .........
MIBG (//) ......
NSE/VMA (//)
204

Maintenance with Cyclo/Topo
Given dose/day
Drug
Dosage
........................mg Topotecan
0.75 mg/m2 IV once daily Day 1-5
........................mg Cyclophosphamide 250 mg/m2/day IV once daily Day 1-5
Day
Topotecan
Cyclophosphamide
Cycle
Cycle
day
1
2
3
4
5
1
2
3
4
5
1
2
3
4
5
Treatment
Cyclophosphamide/Topotecan
Date given
Remarks
NSE/VMA
NSE/VMA
NSE/VMA

CT /MRI (//) .....
Bone scan (//) .........
MIBG (//) ......
NSE/VMA (//)
205

Maintenance with 13 Cis-retinoic acid
Given dose/day
Drug
Dosage
........................mg 13-cis-retinoic acid 80 mg/m2/dose PO BID (total 160 mg/m2/day)
Cycle
1
2
3
4
5
6
Cycle
week
1-2
3-4
5-6
7-8
9-10
11-12
13-14
15-16
17-18
19-20
21-22
Treatment
13-cis-retinoic acid
Off
Off
Off
Off
Off
Date given
Remarks
NSE/VMA
NSE/VMA
NSE/VMA

CT /MRI (//) .....
Bone scan (//) .........
MIBG (//) ......
NSE/VMA (//)
206

Haploidentical donor HSCT (following HD-MIBG) recommended regimen
Day
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
+4
+5
+7
Treatment
Date given
2
Fludarabine 40 mg/m /day IV
Fludarabine 40 mg/m2/day IV
Busulfan 37.5 mg/m2/dose IV every 6 hr
Busulfan 37.5 mg/m2/dose IV every 6 hr
Melphalan 50 mg/m2/day IV
HSC Infusion
Cyclophosphamide* 50 mg/kg IV one dose
Tacrolimus 0.03 mg/kg/day continuous IV
MMF 600 mg/m2 PO twice a day
GCSF 5 mcg/kg/day
until ANC > 2,000/mm3 x 2 SQ
Remarks
* On day +4, Mesna 10 mg/kg/dose will be given pre-cyclophosphamide and then every 3 hours x 4 doses
post cyclophosphamide (total 5 doses).
Tacrolimus and MMF started from day +5
207

Matched-related donor HSCT (following HD-MIBG) recommended regimen
Day
Treatment
Date given
2
-6 Busulfan 37.5 mg/m /dose IV every 6 hr
-5 Busulfan 37.5 mg/m2/dose IV every 6 hr
-2
Cyclosporine 2.5 mg/kg IV every 12 hr
-1 Melphalan 70 mg/m2/day IV
HSC Infusion
0
MMF* 600 mg/m2 PO twice a day
GCSF 5 mcg/kg/day
+5
Remarks
* MMF started from day 0
Cyclosporine started from day -2
208

Autologous HSCT (following HD-MIBG) recommended regimen
Day
Treatment
Date given
2
-6 Busulfan 37.5 mg/m /dose IV every 6 hr
0 HSC Infusion
GCSF 5 mcg/kg/day
+5
Remarks
209

Retinoblastoma
Staging system
International Classification System for Intraocular Retinoblastoma
(Murphree AL: Intraocular retinoblastoma: the case for a new group classification. Ophthalmol Clin North
Am 2005; 18:41-53.)
Group A: Small intraretinal tumors away from foveola and disc
All tumors are 3 mm or smaller in greatest dimension, confined to the retina and
All tumors are located further than 3 mm from the foveola and 1.5 mm from the optic disk
Group B: All remaining discrete tumors confined to the retina
All other tumors confined to the retina not in Group A
Tumor associated with subretinal fluid less than 3 mm form the tumor with no subretinal seeding
Group C: Discrete local disease with minimal subretinal or vitreous seeding
Tumors are discrete
Subretinal fluid, present or past, without seeding involving one fourth of the retina
Local fine vitreous seeding may be present close to discrete tumor
Local subretinal seeding less than 3 mm (2 disk diameters) from the tumor
Group D: Diffuse disease with significant vitreous or subretinal seeding
Tumors may be massive or diffuse
Subretinal fluid present or past without seeding, involving up to total retinal detachment
Diffuse or massive vitreous disease may include greasy seeds or avascular tumor masses
Diffuse subretinal seeding may include plaques or tumor nodules
Group E: Presence of any one or more of these poor prognostic features
Tumor touching the lens
Tumor anterior to the anterior vitreous face involving ciliary body or anterior segment
Diffuse infiltrating retinoblastoma
Neovascular glaucoma
Opaque media from hemorrhage
Tumor necrosis with aseptic orbital cellulites
Phthisis bulbi
Retinoblastoma: Staging system
210

Pathologic classification (pTNM)
(From American Joint Committee on Cancer Retinoblastoma. Manual for staging of cancer. 7th ed, 2010)
Primary Tumour (pT)
pTX: Primary Tumour cannot be assessed.
pT0: No evidence of primary tumour
pT1: Tumour confined to the eye with no optic nerve or choroidal invasion.
pT2: Tumour with minimal optic nerve and / or choroidal invasion:
pT2a: Tumour superficially invades optic nerve head but does not extend past lamina
cribrosa, or tumour exhibits focal choroidal invasion.
pT2b: Tumour superficially invades optic nerve head but does not extend past lamina
cribrosa and tumour exhibits focal choroidal invasion.
pT3: Tumour with significant optic nerve and / or choroidal invasion:
pT3a: Tumour invades optic nerve past lamina cribrosa but not to surgical resection
line, or tumour exhibits massive choroidal invasion.
pT3b: Tumour invades optic nerve past lamina cribrosa but not to surgical resection
line and exhibits massive choroidal invasion.
pT4: Tumour invades optic nerve to surgical resection line or exhibits extra-ocular
extension elsewhere.
pT4a: Tumour invades optic nerve to resection line, but no extra-ocular
extension identified.
pT4b: Tumour invades optic nerve to resection line, and extra-ocular
extension identified.
Regional Lymph Nodes (pN)
pNX: Regional lymph nodes cannot be assessed.
pN0: No regional lymph node metastasis
pN1: Regional lymph node involvement (preauricular, cervical)
pN2: Distant lymph node involvement
Metastasis (pM)
pMX: Presence of metastasis cannot be assessed.
pM0: No distant metastasis
pM1: Metastasis to sites other than Central Nervous System
pM1a: Single lesion
pM1b: Multiple lesions
pM1c: CNS metastasis
pM1d: Discrete masses without leptomeningeal and / or CSF involvement
pM1e: Leptomeningeal and / or CSF involvement
Final Staging ___________________________________________
Retinoblastoma: Pathologic classification (pTNM)
211

Investigations
Examination
-Examination under anesthesia by ophthalmologist

-Audiology evaluation (hearing test) if systemic carboplatin is considered
Imaging studies
-CT or MRI scan of brain and orbit should include the pineal gland to
exclude trilateral retinoblastoma ( prefer MRI to avoid radiation exposure)
Laboratory evaluations -CBC
-BUN, Cr, electrolytes, Ca, Mg, P, LFT
-Calculated creatinine clearance
-Urine analysis
Diagnostic studies
-Lumbar puncture only when there is radiographic or clinical suspicion of
CNS disease ie. optic nerve involvement or stage pT2
-Bone scan only with bone pain or other extraocular disease
-Bone marrow aspiration and biopsy only when there is abnormal blood
counts (without alternative explanation) or other extraocular disease
-Pathologic evaluation if enucleation is performed.
Indications of enucleation
1. Large tumor >50% of globe volume (ICRB group E, + D)
2. No potential for visions
3. Painful eyes
4. Optic nerve involvement
Laser photocoagulation and cryotherapy
For ICRB Group A: repeat every 3-4 weeks until evidence of tumor regression and inactivity (indirect
fundoscopy showing flat scar (or type IV regression pattern) along with the absence of new tumor foci,
evidence of tumor recurrence, or evidence of subretinal fluid, subretinal seeds, or vitreous seeds).
External beam radiation therapy (EBRT: lens sparing EBRT vs whole eye EBRT)
Standard dose is 40-45 Gy, preferably conformal, stereotactic, proton-beam or intensity-modulated
radiotherapy, and delayed to after 1 year of age with use of systemic adjuvant chemotherapy to avoid risk of
secondary malignancy
Family screening
Evaluation
Schedule
Eye examination for -Parents and siblings of patients should have screening ophthalmic
parents and siblings examinations to exclude an unknown familial disease.
-Siblings should be under close surveillance until age 3 to 5 years (every 1-2
months during the first year, then every 2 months during the second year,
then every 4-6 months during the third year, then once or twice a year until
age 5, after that follow as general population ) or until confirmed not to have
a genetic mutation.
Retinoblastoma: Investigations
212

Summary treatment strategy based on laterality and retinoblastoma grouping
International
Classification
Unilateral
of
Retinoblastoma
A
Laser or cryotherapy
B/C
CEV or plaque + Laser or cryotherapy
D
Enucleation or CEV + SCC + Laser or
cryotherapy
E
Enucleation
Bilateral*
Laser or cryotherapy
CEV + Laser or cryotherapy
CEV + SCC + Laser or cryotherapy
Enucleation but if both eyes equally
advanced then CEC + SCC + Laser
or cryotherapy + low dose EBRT
* Treatment in bilateral cases is usually based on the most advanced eye, Laser, laser photocoagulation; EBRT, external beam
radiotherapy; plaque, plaque radiotherapy; SCC, subconjuctival carboplatin; CV, vincristine, carboplatin plus thermotherapy or
cryotherapy; CEV, vincristine, etoposide, carboplatin plus thermotherapy or cryotherapy.
Note: May consider ICEV instead of CEV+SCC

Chemotherapy should be perform within 24 hours of local treatment by ophthalmologist
On the basis of the International Classification of Retinoblastoma, chemoreduction success is achieved in eye
survival rate 100% of group A, 93% of group B, 90% of group C, 47% of group D eyes, and 0% of group E.
Reference
Adapted from Carol L, Shields and Jerry A. Shields. Basic understanding of current classification and
management of retinoblastoma. Current Opinion in Ophthalmology 2006; 17: 228 234.
ARET0331 progress report 22/01/2010 closure of trial of systemic neoadjuvant chemotherapy for
group B intraocular retinoblastoma
The regression pattern (examined by EUA) after treatment:
Type I is calcification.
Type II is fish flesh lesion.
Type III is mixed type I and II.
Type IV is flat scar.
Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping
213

Schematic treatment for intraocular retinoblastoma
Unilateral retinoblastoma
-ICRB group E ie.Large tumor > 50% of globe volume
-No potential for visions
-Painful eyes
-Optic nerve involvement
Yes
No
ICRB Group A
ICRB Group B, C
Cryotherapy
and/or
Laser therapy
Chemotherapy Protocol
ThaiPOG-RB-I3-01
(Carbo/Eto/VCR)
X 6 cycles
ICRB Group D
Enucleation
ThaiPOG-RB-13-02
(Ifos/Carbo/Eto/VCR)
X 6-8 cycles
High risk features: assessed by pathologist

-Anterior chamber seeding
-Optic nerve tumor beyond lamina cribosa, but not to surgical margin
-Choroidal involvement
-Intraocular hemorrhage
-Posterior uveal involvement with any optic nerve disease (optic nerve
head, pre or postlaminar cribosa)
Yes
No
Enucleation or EBRT
if not fully responded
Low risk
High risk
Schedule regular
fundoscopic
examination
ThaiPOG-RB-13-01
(Carbo/VCR/Eto)
X 6 cycles
214

Schematic treatment for extraocular retinoblastoma
Extraocular retinoblastoma
Regional disease
- Disease at the surgical margin
- Orbital recurrence (orbital mass)
- Tumor in an emissary canal
(intrascleral involvement)
- Episcleral disease
- Positive pre-auricular lymph nodes
Enucleation
Metastatic diasese: CNS, bone, bone

marrow involvement
- Isolated meningeal disease
- Ectopic intracranial retinoblastoma
Chemotherapy ThaiPOG-RB-13-04
(ICE protocol every 4 weeks x 6-8 cycles)
plus IT chemotherapy (ThaiPOG-RB-13-05) if positive CSF cytology
EBRT at orbit at week 6 + Chemotherapy

Protocol ThaiPOG-RB-13-03
(VCR/Ida/CTX alternate Eto/carbo
every 3 weeks x 4 cycles)
Myeloablative chemotherapy and

autologous stem cell rescue
EBRT for bulky disease at week 6 of SCT
215

Post-treatment evaluation
For patients with preserved eye
Evaluation
Schedule
Eye examination under
anesthesia (EUA)
MRI brain and orbit
Note
- Every 3-4 weeks until no active tumor on minimum 3

EUAs
-Then every 6-8 weeks until 3 years of age
-Then every 4-6 months until 10 years of age
-Then yearly
-Every 6-12 months until 5 years of age
For patients after enucleation and/or received EBRT

Evaluation
Schedule
Eye examination under
anesthesia (EUA)
Patients should be
examined without
anesthesia when old
enough to cooperate.
Note
-At 4-6 weeks post treatment

-Then every 2-3 months in year 1
-Then every 3-4 months in year 2
-Then every 6 months until 5 years of age
-Then yearly
Patients should be
examined without
anesthesia when old
enough to cooperate.
For patients with extraocular disease

Evaluation
Schedule
Note
CT or MRI of the brain and

orbits
CSF profiles and cytology
Every 6 months in first 3 years then every year until 5

years after off treatment
Every 6 months in first 3 years then every year until 5
years after off treatment
Bone marrow aspiration and If unexplained cytopenia or bone scan positive
biopsy
Bone scan
-Every 1 year for first 3 years
- prefer MRI to avoid

radiation exposure
For patients with bilateral retinoblastoma, esp. whom diagnosed before 1 year of age or positive family
history
Evaluation
Schedule
Note
CT or MRI of the brain and
orbits
Every 6 months from the end of treatment until 5 years

of age
- Screen for trilateral

retinoblastoma
- prefer MRI to avoid
radiation exposure
For patients who received chemotherapy and/or radiation therapy

Evaluation
Schedule
Note
History and physical
examination
-Every 3 months until 2 years off treatment

-Then every 6 months until 5 years off
treatment
-Then yearly
Visual acuity assessment

CBC
-Yearly
-Yearly for 10-15 years from exposure of
chemotherapy
Retinoblastoma: Post-treatment evaluation
- Late effects of treatment

- Growth and development
- Surveillance for second malignant
neoplasms (osteosarcoma, soft tissue
sarcomas, skin cancers, breast
cancers)
-Surveillance for secondary leukemia
216

Treatment Protocol for Retinoblastoma
Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...................................
History
Presenting S&S
leukocoria
orbital mass
eye pain
Others.................
Prenatal History
X-ray exposure
Medication....
Illness..chemical exposure......
Others...
Cancer in family
None
Retinoblastoma other cancers....
Pedigree

A. Blood date (//)
CBC ....
3
*start each course of chemotherapy when ANC > 1,000/mm
BUN Creatinine LDH SGOT SGPT Alk Phos

Na K .. Cl HCO3 Ca .. Mg.
B. Imaging study
CT/ MRI orbit and brain with contrast (//) ......
Chest X-Ray (//..) Result positivenegative

Lumbar Puncture : CSF cell count and cytospin (../../..) Result positive. negative
Bone scan (//..) Result positivenegative
* For patient with bone pain or extraocular disease only

Bone marrow aspiration* : Wright stain smear and clotted marrow sent for pathological review
(//)
Result positive
negative
*For patient with unexplained cytopenia or extraocular disease only
BMA/ biopsy (//) ....

Retinoblastoma: Data entry form
217

Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01]
Protocol name ThaiPOG-RB-13-01
Protocol for Retinoblastoma ICRB group B, C or Post enucleation with high risk features
Reference
Orkin SH,et al. Oncology of Infancy and Childhood, 1st ed, 2009. P 576-601.
Lanzkowsky P. Manual of Ped Hematology and Oncology, 5th ed, 2011. P.759-775
Open Date
January 2014
Inclusion criteria
Retinoblastoma ICRB group B
Retinoblastoma ICRB group C
Retinoblastoma post enucleation with high risk features
Anterior chamber seeding
Optic nerve tumor, but not to surgical margin
Choroidal involvement
Intraocular hemorrhage
Posterior uveal involvement with any optic nerve disease
Given dose
_______mg
Drug
Vincristine
_______mg
_______mg
Carboplatin
Etoposide
Dosage
0.05 mg/kg or 1.5 mg/m2/day in NSS IV slowly push
(max 2 mg)
18.6 mg/kg or 560 mg/m2/day in D5W IV in 15-30 min
5 mg/kg or 150 mg/m2/day IV in D5W IV in 60 min
Day
1
1
1, 2
*In patient BW < 12 kg, use doses per kg
Give chemotherapy every 28 days for total 6 courses

Give G-CSF 5 mcg/kg SC daily in subsequent course of chemotherapy that results in neutropenia
(to be started on day 3, at least 24 hours from last dose of chemotherapy, until ANC > 1,000/mm3)
Criteria for starting chemotherapy:
o Absolute neutrophil count >1,000/ mm3
o Platelet count >100,000/ mm3
o ALT <10 the upper limit of normal
o Normal glomerular filtration rate
Record BP q 15 min during etoposide infusion

Fundoscopic examination by ophthalmologist before each cycle
Hearing exam before starting chemotherapy, at cycle 3 or 4 and end of treatment (Optional)
Consider enucleation or EBRT if patient does not fully respond to chemotherapy
Retinoblastoma: Treatment protocol for retinoblastoma [ThaiPOG-RB-13-01]
218

Schedule of chemotherapy Protocol ThaiPOG-RB-13-01
Course
Date
BW / BSA
Dose adjusted
Note
1
2
3
4
5
6
219

Protocol for Retinoblastoma ICRB group D/ E
Reference
SH Lee. et.al, Bone Marrow Transplantation 2008; 42: 385-391
Open Date
January 2014
Inclusion criteria
Retinoblastoma ICRB group D
Retinoblastoma ICRB group E
Given dose
_______mg
_______mg
_______mg
Drug
Ifosfamide
Etoposide
Mesna
Dosage
60 mg/kg or 1,800 mg/m2/day in NSS IV drip in 30-60 min
5 mg/kg or 150 mg/m2/day in D5W IV drip in 60 min
20 mg/kg or 600 mg/m2/dose IV drip in 15 min before
Ifosfamide then at 3, 6 hr after Ifosfamide (total 3 doses)
_______mg Carboplatin 18.6 mg/kg or 560 mg/m2/day in D5W IV drip in 15-30 min
_______mg Vincristine 0.05 mg/kg or 1.5 mg/m2 in NSS IV slowly push (max 2 mg)
Day
0, 1, 2
0, 1, 2
0, 1, 2
0
0
* start G-CSF 5 mcg/kg __________ mcg OD after completion of chemotherapy 24 hr

** Hydration following high dose cyclophosphamide/ Ifosfamide guideline
Give chemotherapy every 4 weeks until the tumor disappear, or until local therapy can control the
tumor
Record water intake/ output and give diuretic if necessary
Check CBC, BUN, Cr, Electrolyte, Ca2+, Mg2+, PO4 and LFT before start each course
Consider hearing exam peroidically
220

Course
Date
BW / BSA
Dose adjusted
Note
1
2
3
4
5
6
7
8
9
10
11
12
221

Protocol for Extraocular Retinoblastoma: Regional disease
Reference
Chantada G, et.al. Cancer 2004;100(4): 834-842.
Open Date
January 2014
Inclusion criteria
Disease at the surgical margin
Orbital recurrence (orbital mass)
Tumor in an emissary canal (intrascleral involvement) Episcleral disease
Positive pre-auricular lymph nodes
Evaluation extent of disease before treatment
Imaging studies .............................................................................................................................................
Bone scan .....................................................................................................................................................
CSF studies ...........................................................................................................................................
BMA ..............................................................................................................................................................
Chemotherapy schedule
Week
0
3
6
9
12
15
Course
A1
B1
A2
B2
A3
B3
Date
***** Start G-CSF at 24 -48 hr after completion each course of chemotherapy *****
Course A
Given dose
__________mg
__________mg
__________mg
__________mg
Drug
Vincristine
Idarubicin
Cyclophosphamide*
Mesna
Dosage
0.05 mg/kg or 1.5 mg/m2 IV slowly push
0.33 mg/kg or 10 mg/m2 IV infusion in 60 min
65 mg/kg or 2,000 mg/m2 IV drip in 30-60 min
30 mg/kg or 1,000 mg/m2 IV drip in in15 min
at 0,3 hr after CTX (total 2 doses)
18
A4
21
B4
Day
1
1
1
1
In patient BW < 12 kg, use doses per kg
* hydration following High dose CTX guideline

Course B
Given dose
__________mg
__________mg
Drug
Etoposide
Carboplatin
Dosage
3.3 mg/kg or 100 mg/m2 IV drip in 60 min
18.6 mg/kg or 560 mg/m2 IV drip in 15-30 min
Day
1-3
1-2
In patient BW < 12 kg, use doses per kg
222

Record water intake/ output and give diuretic if necessary.
Consider hearing exam periodically
Course
Date
BW / BSA
Dose adjusted
Note
A1
B1
A2
B2
A3
B3
A4
B4
223

Protocol for Metastasis retinoblastoma
Open Date
January 2014
Inclusion criteria
Retinoblastoma with CNS/ bone/ bone marrow involvement
Retinoblastoma with isolated meningeal disease
Ectopic intracranial retinoblastoma
Given dose
___________mg
___________mg
___________mg
Drug
Carboplatin
Ifosfamide
Mesna
___________mg
Etoposide
Dosage
18.6 mg/kg or 560 mg/m2/day in D5W IV drip in 15-30 min
60 mg/kg or 1,800 mg/m2/day in NSS IV drip in 30-60 min
15 mg/kg or 450 mg/ m2/dose IV drip in 15 min before
Ifosfamide, then at 3, 6, 9 hours post Ifosfamide (total 4
doses)
3.3 mg/kg or 100 mg/m2/day in D5W IV drip in 60 min
Day
1
1-5
1-5
1-5
* start G-CSF 5 mcg/kg __________ mcg OD after completion of chemotherapy 24 hr

** Hydration following high dose Cyclophosphamide/ Ifosfamide guideline
Give chemotherapy every 4 weeks

Record water intake/output and give diuretic if necessary
Consider myeloablative chemotherapy and autologous stem cell rescue
EBRT for bulky disease at week 6 of SCT
224

Schedule of chemotherapy Protocol Thai-POG-13-04
Course
Date
BW / BSA
Dose adjusted
Note
1
2
3
4
5
6
7
8
225

Treatment protocol for intrathecal in retinoblastoma [ThaiPOG-RB-13-05]
Protocol for Retinoblastoma with CNS involvement
Reference
Adapted from Orkin's Oncology of Infancy and Childhood 1st ed, 2009 p.576-601
Open Date
January 2014
Patients name..................................................................... Sex.................. HN...........................................
* age adjusted dose intrathecal
chemotherapy
Methotrexate
Ara-C
< 4mo
4 11 mo
12-23 mo
24-36 mo
>36 mo
3
10
6
20
8
30
10
50
12
70
Give IT chemotherapy until CSF is negative 2 times consecutively with minimum 4 doses
Cycle
week/ date given
CSF result
1
week 0/
week 1/
week 2/
week 3/
week 4/
week 5/
week 6/
week 7/
week 8/
week 9/
week 10/
week 11/
week 12/
week 13/
week 14/
week 15/
Retinoblastoma: Treatment protocol for intrathecal in retinoblastoma [ThaiPOG-RB-13-05]
226

Renal tumor
Staging system for renal tumors
Stage
I
NWTSG (before chemotherapy)

(a) Tumor is limited to the kidney and
completely excised
(b) The tumor was not ruptured before or during
removal
(c) The vessels of the renal sinus are not
involved beyond 2 mm
(d) There is no residual tumor apparent beyond
the margins of excision
II
(a) Tumor extends beyond the kidney but is

completely excised
(b) No residual tumor is apparent at or beyond
the margins of excision
(c) Tumor thrombus in vessels outside the
kidney is stage II if the thrombus is removed en
bloc with the tumor
III
Residual tumor confined to the abdomen:

(a) Lymph nodes in the renal hilum, the
periaortic chains, or beyond are found to
contain tumor
(b) Diffuse peritoneal contamination by the
tumor
(c) Implants are found on the peritoneal
surfaces
(d) Tumor extends beyond the surgical margins
either microscopically or grossly
(e) Tumor is not completely resectable
because of local infiltration into vital structures
IV
Presence of hematogenous metastases or

metastases to distant lymph nodes
(a) Tumor extends beyond the kidney but is

completely excised
Note: ThaiPOG NWTSG staging
V
Renal tumor: Staging system for renal tumors
SIOP (after chemotherapy)

(a) Tumor is limited to kidney or surrounded
with fibrous pseudocapsule if outside of the
normal contours of the kidney, the renal capsule
or pseudocapsule may be infiltrated with the
tumor, but it does not reach the outer surface,
and is completely resected (resection margins
clear)
(b) The tumor may be protruding into the pelvic
system and dipping into the ureter (but it is not
infiltrating their walls)
(c) The vessels of the renal sinus are not
involved
(d) Intrarenal vessel involvement may be
present
(a) The tumor extends beyond kidney or
penetrates through the renal capsule and/or
fibrous pseudocapsule into perirenal fat but is
completely resected (resection margins clear)
(b) The tumor infiltrates the renal sinus and/or
invades blood and lymphatic vessels outside the
renal parenchyma but is completely resected
(c) The tumor infiltrates adjacent organs or vena
cava but is completely resected
(a) Incomplete excision of the tumor, which
extends beyond resection margins (gross or
microscopical tumor remains postoperatively)
(b) Any abdominal lymph nodes are involved
(c) Tumor rupture before or intraoperatively
(irrespective of other criteria for staging)
(d) The tumor has penetrated through the
peritoneal surface
(e) Tumor thrombi present at resection margins
of vessels or ureter, transsected or removed
piecemeal by surgeon
(f) The tumor has been surgically biopsied
(wedge biopsy) prior to preoperative
chemotherapy or surgery
Hematogenous metastases (lung, liver, bone,
brain, etc.) or lymph node metastases outside
the abdomino-pelvic region
Bilateral renal tumors at diagnosis
227

Protocol assignment
Histology
Favorable histology
(FH)
Focal anaplasia
Diffuse anaplasia
Clear cell sarcoma
(CCSK)
Stage I
Regimen E
Stage II
Regimen E
Stage III
Regimen D
Stage IV
Regimen D
Regimen D
Regimen D
Regimen I
Regimen D
Regimen I
Regimen I
Regimen D
Regimen I
Regimen I
Regimen D
Regimen I
Regimen I
Radiation therapy dosing guidelines (within 10-14 days after surgery)

Tumor Characteristics
Stage I and II FH Wilms tumor
Stage I-II FA or DA or CCSK
Stage III FH or CCSK of FA
Cytology-positive ascites or preoperative rupture or
diffuse operative tumor spillage
Residual gross disease >3 cm
Stage III DA
Stage I-III RTK
Recurrent abdominal Wilms tumor
Radiation Dose/Field
None
10.5 Gy flank
10.5 Gy flank
10.5 Gy WAI
10.8 Gy boost to residual disease
20 Gy flank or WAI, as for ascites or rupture above
12.6-18 Gy (<12 months of age), or 21.6 Gy (older

children) if previous rediation dose is <10.8 Gy.
Boost dose of up to 9 Gy to gross residual tumor
after surgery
Lung metastases
12 Gy whole lung in 8 fractions (1,050 cGY if <12
months age)
Brain metastases
30.6 Gy whole brain in 17 fractions, or 20 Gy whole
brain + 10-15 Gy IMRT or stereotactic boost
Liver metastases
19.8 Gy whole liver in 11 fractions
Bone metastases
25-30 Gy to the lesion plus 3-cm margin
Lymph node metastases
19.8 Gy to lymph nodes in 17 fractions
FH, Favorable histology; FA, focal anaplasia; DA, diffuse anaplasia; CCSK, clear cell sarcoma of the kidney;
WAI, whole abdomen irradiation; RTK, rhabdoid tumor of kidney; IMRT, intensity-modulated radiotherapy.
Note: 1. Actinomycin-D and doxorubicin doses should be decreased 50% if given withn 6 weeks following
whole- lung or whole-abdomen RT.
2. Pneumocystie jiroveci prophylaxis with cotrimoxazole or pentamidine should be instituted in patients
receiving lung RT.
Renal tumor: Protocol assignment
228

Treatment protocol for Wilms tumor [ThaiPOG-WT-13-01]
Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2
() ...................................
History
Histology
Favorable histology (FH)
Stage I
Regimen E
Stage II
Regimen E

A. Blood date (//)
CBC ........
BUN Creatinine Electrolyte.
LFT...
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) ..........
* Use the same imaging modality CT or MRI for all disease evaluations.
Renal tumor: Treatment protocol for Wilms tumor [ThaiPOG-WT-13-01]
229

Treatment Protocol for Wilms tumor
Protocol name ThaiPOG-WT-13-01
Protocol for Favorable histology
Reference
NWTS-5, Regimen E
Open Date
January 2014
Age (yy/mm).............................. BW...........................kg HT...............................cm BSA.........................m2
Drug Dose Information
AMD = Actinomycin-D X 1day
Age < 12 months

0.023 mg/kg IV
Dosage
Age 12 months
0.045 mg/kg IV
VCR1 = Vincristine X 1day
0.025 mg/kg IV
0.05 mg/kg IV
VCR2 = Vincrintine X 1day
0.034 mg/kg IV
0.067 mg/kg IV
Drug
Week
Date
BSA
AMD
VCR1
BW 30 kg
1.35 mg/M2 IV
(Maximum dose 2.3 mg)
1.5 mg/M2 IV
(Maximum dose 2 mg)
2 mg/M2 IV
(Maximum dose 2 mg)
VCR2
Note
0
1
2
Evaluate: date (/....../..) CBC ........
LFT...
3
4
5
LFT...
6
7
8
230

Week
Date
BSA
AMD
VCR1
VCR2
Note
LFT...
9
10
LFT..
Chest X-Ray (//) .....
12
LFT....
15
18
Post- treatment investigations.
A. Blood date (//) CBC ......
LFT...
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) ..........
*Use the same imaging modality CT or MRI for all disease evaluations.
231

Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...................................
History
Histology
Favorable histology (FH)
Focal anaplasia
Diffuse anaplasia
Stage I
Regimen D
Regimen D
Stage II
StageIII
StageIV
Regimen D Regimen D
Regimen D Regimen D Regimen D

A. Blood date (//)
CBC .......
BUN Creatinine Electrolyte
LFT..
B. Imaging study
CT chest (//) ....
.
Chest X-Ray (//) ...
CT/ MRI abdomen* (//) .........
232

Protocol for Favorable histology and anaplasia
Reference
NWTS-5, Regimen D
Open Date
January 2014
Age < 12 months

0.023 mg/kg IV
Dosage
Age 12 months
0.045 mg/kg IV
0.025 mg/kg IV
0.05 mg/kg IV
0.034 mg/kg IV
0.067 mg/kg IV
DOX1 = Doxorubicin X 1day

DOX2 = Doxorubicin X 1day
0.75 mg/kg IV
0.5 mg/kg IV
1.5 mg/kg IV
1 mg/kg IV
Drug
Week
Date
BSA
AMD
VCR1
VCR2
BW 30 kg
1.35 mg/M2 IV
(Maximum dose 2.3 mg)
1.5 mg/M2 IV
(Maximum dose 2 mg)
2 mg/M2 IV
(Maximum dose 2 mg)
45 mg/M2 IV
30 mg/M2 IV
DOX1
DOX2
Note
*XRT
1
2
LFT...
** XRT start by Day 10 post-nephrectomy (no later than Day 14)
3
4
5
LFT...
6
7
8
233

Week
Date
BSA
AMD
VCR1
VCR2
DOX1
DOX2
Note
LFT...
9
10
11
LFT...
CT chest$ (//) ......
$for patients with pulmonary metastases at diagnosis only.
..
..
..
Chest X-Ray (//) .......
CT/ MRI abdomen* (//) ..........
EKG/ECHO (//) .........
12
13
14
LFT...
15
16
17
LFT...
18
19
20
LFT...
234

Week
Date
BSA
AMD
VCR1
VCR2
DOX1
DOX2
Note
21
22
23
LFT...
24
25
26
A. Blood date (//)
CBC .......
LFT..
B. Imaging study
CT chest (//) ......
..
Chest X-Ray (//) .......
Abdominal Ultra Sound (//) .....
CT/ MRI abdomen* (//) ...........
EKG/ECHO (//) .........
#at baseline abdominal US and Doppler recommended but not require excluding IVC tumor thrombus
235

Data entry form
Date of Birth........................................ Date of Diagnosis................................... ....................
Address...........................................................................................................................................................
..............................................................................Contact person....................................Tel........................
Age (yy/mm/dd)................................ BW................................ HT................................ BSA.........................
Father............................................................................ Age........................... Occupation...........................
Mother............................................................................ Age........................... Occupation...........................
History
Histology
Diffuse anaplasia
Clear cell sarcoma (CCSK)
Stage I
Regimen I
Stage II
Regimen I
Regimen I
StageIII
Regimen I
Regimen I
StageIV
Regimen I
Regimen I

A. Blood date (//)
CBC ......
LFT..
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) .....
CT/ MRI abdomen* (//) .........
236

Protocol for Diffuse anaplasia and Clear cell sarcoma
Reference
NWTS-5, Regimen I
Open Date
January 2014
Drug
DOX = Doxorubicin X 1day
Age < 12 months

0.75 mg/kg IV
0.025 mg/kg IV
0.034 mg/kg IV
CTX5 = Cyclophophamide X 5 days 7.35 mg/kg/day

CTX3 = Cyclophophamide X 3 days
ETOP = Etoposide X 5 days
1.65 mg/kg/day
Week
Date
BSA
DOX
VCR1
VCR2
Dosage
Age 12 months BW 30 kg
1.5 mg/kg IV
45 mg/M2 IV
0.05 mg/kg IV
1.5 mg/M2 IV
(Maximum dose 2 mg)
0.067 mg/kg IV
2 mg/M2 IV
(Maximum dose 2 mg)
14.7 mg/kg/day
440 mg/M2/day
3.3 mg/kg/day
CTX5
CTX3
100 mg/M2/day
ETOP
Note
*XRT
1
2
Evaluate: date (/....../..) CBC ......
BUN Creatinine Electrolyte..
LFT...
* XRT start by Day 10 post-nephrectomy (no later than Day 14)
3
4
5
LFT...
237

Week
Date
BSA
DOX
VCR1
VCR2
CTX5
CTX3
ETOP
Note
6
7
8
LFT...
9
10
11
Evaluate: date (/....../..) CBC .........
LFT....
CT chest$ (//) .....
$for patients with pulmonary metastases at diagnosis only.
..
..
..
Chest X-Ray (//) .......
CT/ MRI abdomen* (//) ...........
EKG/ECHO (//) .........
12
13
14
LFT...
15
16
17
LFT...
18
19
20
238

ETOP
Week Date
BSA
DOX
VCR1
VCR2
CTX5
CTX3
Note
LFT...
21
22
23
LFT...
24
25
26
A. Blood date (//)
CBC ......
LFT....
B. Imaging study
CT chest (//) ......
..
Chest X-Ray (//) .......
Abdominal Ultra Sound (//) .....
CT/ MRI abdomen* (//) ...........
EKG/ECHO (//) .........
#at baseline abdominal US and Doppler recommended but not require excluding IVC tumor thrombus
239

Data entry form
Address...........................................................................................................................................................
Age ............. yr...............m.
BW...........kg
Ht...............cm.
BSA...................m2

() ...................................
History
Histology
Stage
FH
I
Focal anaplasia
II
Diffuse anaplasia
III
IV
Clear cell Sarcoma

V

A. Blood date (//)
CBC .......
LFT..
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) .........
240

Protocol name ThaiPOG-WT-13-VHR
Protocol for Bilateral Wilms tumor
Reference
NWTS-5, Bilateral Wilm tumor
Open Date
January 2014
Inclusion criteria
Initial treatment with VAD 6 weeks then reevaluate
1. If bilateral partial nephrectomy feasible Definite surgery at week 6
2. If bilateral partial nephrectomy NOT feasible
a. partial response in both kidney continue VAD for 6 weeks
i. Definite surgery at Week 12
ii. Complete response Start regimen D
b. < partial response in either kidney
i. Bilateral open biopsy at week 6
3. If complete response in both kidney start regimen E
Age < 12 months

0.023 mg/kg IV
VCR = Vincristine X 1day
0.025 mg/kg IV
Dosage
Age 12 months
0.045 mg/kg IV
(Maximum 2.3 mg)
0.05 mg/kg IV
DOX = Doxorubicin X 1day
1.2 mg/kg IV
35 mg/M2 IV
Week
AMD
Drug
Date
BSA
VCR
DOX
Age 3 years
1.5 mg/M2 IV
(Maximum dose 2 mg)
Note
0
1
2
3
4
5
241

242

Post- treatment investigations
A. Blood date (//)
CBC ........
LFT...
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) .........
*Use the same imaging modality CT or MRI for all disease evaluations.
243

(Recommended imaging studies for follow-up)
Favorable-histology Wilms' without metastatic disease,
1. CXR + abdominal U/S alternate with CXR + abdominal/pelvic CT q 3 months during first 3 years.
2. CXR + U/S q 6 months for 2 years (in 4th + 5th year)
Wilms' with metastatic or anaplastic disease;
1. CXR + abdomen/pelvic CT q 3 months x 2 years
2. CXR + U/S q 6 months in 3rd to 5th year
Bilateral Wilms' tumor or nephrogenic rest;
Abdominal ultrasound examinations should be performed every 3 months until age 8.
Renal tumor: (Recommended imaging studies for follow-up)
244

Hepatoblastoma
Data entry form for hepatoblastoma
Name
Address
Father
Mother
Birth weight
Date Registered
Age
Sex
History
HN
DOB
Age
Occupation
Age
Occupation
Gestational age
Pre-treatment Investigations
A. Imaging study
CT scan liver (___/___/___)
CXR PA/lateral (___/___/___)

CT chest (___/___/___)
Bone scan (Optional) (___/___/___)
B. CBC (___/___/___)
C. Tumor Markers (___/___/___)
AFP
D. Blood chemistry (___/___/___) BUN Cr
HCO3
Ca
P
Mg
AST
E.
F.
G.
H.
I.
J.
GFR ( calculated / measured)

Coagulogram (___/___/___) PT
Hepatitis profile (___/___/___)
EKG (___/___/___)
Audiogram (___/___/___)
Other (___/___/___)
-HCG
uric acid
ALT DB
Na
TB
LDH
K
AP
C
GGT
ml/min/1.73m2
aPTT
Hepatoblastoma: Data entry form for hepatoblastoma
fibrinogen
245

PRETEXT (Pre-treatment extent of disease) staging system
PRETEXT is based upon division of the liver into

four sections.
Section 1 (left lateral) : Couinaud 2 and 3
Section 2 (left medial) : Couinaud 4
Section 3 (right anterior) : Couinaud 5 and 8
Section 4 (right posterior) : Couinaud 6 and 7
In addition any group may have:

V : invasion vena cava or all 3 major hepatic veins
P : invasion main portal vein or bifurcation
E : intra-abdominal extrahepatic extension
M : distant metastasis
C : caudate lobe involvement
PRETEXT I
PRETEXT II
PRETEXT III
PRETEXT IV
=
=
=
=
One section is involved, three contiguous sections free of tumor

Two sections involved, two contiguous sections free of tumor
Two or three sections involved, no two adjoining sectors free of tumor
All four sections involved, no section free of tumor
Pretreatment diagnosis : Hepatoblastoma PRETEXT __________
Indication for biopsy

1. Age <6 months, or >3 years
Biopsy is mandatory because of the wide differential diagnosis of hepatic

masses and the possible confounding effect of an elevated serum AFP level
if age <6 months, and because of the risk of misdiagnosing hepatocellular
carcinoma if age >3 years
2. Age 6 months - 3 years
Biopsy is not required if typical radiological finding of hepatoblastoma and

elevated AFP (>100 ng/ml) are present
Hepatoblastoma: PRETEXT (Pre-treatment extent of disease) staging system
246

High dose cisplatinum (CDDP) administration protocol
1. CDDP
electrolytes, Ca, Mg, BUN creatinine, U/A
GFR Schwartz formula
GFR (ml /min /1.73 m2) =
k x Height cm
Serum cr mg / dL
k = 0.33 (infant with Hx LBW), 0.45 (infant), 0.55 (child or adolescent girl), 0.7 (adolescent boy)
GFR > 60 ml /min /1.73 m2
2. 4 .
Hydration 5%D NSS/_____ (Vol ______ml/bottle) + KCl (10 mEq/L) _____ ml
+ MgSO4 (8 mEq/L) _____ml IV drip at rate _____ /hr (125 ml /m2 /hr) x 4 hr
Hour 0
record I/O
4-6 .
: 5%D NSS/_____ , Vol ________ ml
+ CDDP
mg (80 mg /m2)
+ mannitol
gm (500 mg /kg)
+ KCl
ml (1 mEq /kg)
IV at rate
ml /hr (125 ml /m2 /hr) x 24 hr
( CDDP 3-4 ml /kg /hr mannitol 200 mg /kg in 25 ml

NSS IV over 15 min 1 . lasix 0.5 mg /kg )
Hour 24
CDDP IV fluid
5%D NSS/_____ (Vol ________ml/bottle)
+ KCl (10 mEq/L) _____ ml + MgSO4 (8 mEq/L) _____ml
IV drip at rate _____ /hr (125 ml /m2 /hr) x 12 hr
ml /hr ( 65 ml /m2 /h )
rate IV
3. Oral Mg supplement : Minimal daily requirement = 0.3 mEq /kg /d (12 mg Mg = 1 mEq)
Mag oral tab
= 7
mEq Mg / tab
Milk of Magnesia
= 13
mEq Mg / 5 ml
Mg sulfate solution 50%
= 20
mEq / 5 ml
Hepatoblastoma: High dose cisplatinum (CDDP) administration protocol
247

1. Monitor AFP level
- Every 2 months in the 1st year
- Every 3 months in the 2nd year
- Every 4 months in the 3rd year
- Every 6 months in the 4th year
2. Hearing test
- Pretreatment
- Before delayed surgery
- At the end of treatment
- At 1 year after treatment
3. Echocardiogram/ MUGA scan
- Yearly for 4 years in patient who received Doxorubicin
4. Imaging
- CT chest/abdomen is not necessary if AFP > 100 ng/ml at the time of diagnosis
- In patient with low AFP (< 100 ng/ml) at diagnosis, CT chest/abdomen should be performed
- Every 3 months for 2 year
- Every 4 months in the 3rd year
- Every 6 months in the 4th year
- CT abdomen can be used in alternate sequence with U/S abdomen only if high resolution U/S
abdomen is available
Hepatoblastoma: Post-treatment evaluation
248

Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR]
1. Patient of PRETEXT I, II, III without any high risk features (+V, P, E, M or AFP <100 ng/ml) will be
proceed to upfront surgery if gross total tumor removal can be achieved. Patient who found to have V/P/M
involvement in the operative field will be shifted to high risk group (HR) irrespective of the PRETEXT staging.
2. Classify tumor into 4 groups (VLR, LR, IR, HR) according to PRETEXT, AFP, surgery and pathology
result.
3. Very low risk patient does not require chemotherapy.
Hepatoblastoma: Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR]
249

Protocol name
Protocol for
Open date
Modified from
ThaiPOG-HB-13-VLR
Very low risk hepatoblastoma
January 2014
N Engl J Med 2009;361:1662-70
Patient eligibility
Exclusion criteria
PRETEXT I, II, III with total tumor removal, and pure fetal histology (PFH) AFP < 100 ng/ml
tumor with high risk features (+V/P/E/M)
Patients name
BW
Age
Ht
Sex
HN
BSA
Initial surgery ( Date _____/_____/_____ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other_________________________
section # ______________ result _______________________________________________________________
Hepatoblastoma: Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR]
250

Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR]
result.
3. First course of chemotherapy should be started within 7-14 days after the diagnosis
4. If CT chest is not available before the treatment, it MUST be done no later than 14 days after starting of
the first course of chemotherapy
5. Chemotherapy will be given every 2 weeks for 4 courses
6. Hearing test should be performed at pre-treatment, before surgery, end of treatment and 1 year post off
treatment
Anti-emetic guideline
1. Ondansetron 5 mg/m2/dose IV pre-chemo and then q 8 hr PLUS
2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) IV drip in 10 min pre-chemo, then q 12 hr
Note Aprepitant 125 mg po on day 1, then 80 mg po daily on day 2,3 may be given as an additional antiemetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.
Hepatoblastoma: Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR]
251

Protocol name
Protocol for
Open date
Modified from
ThaiPOG-HB-13-LR
Low risk hepatoblastoma
January 2014
N Engl J Med 2009;361:1662-70
Patient eligibility
PRETEXT I, II, III with total tumor removal
(non PFH & non SCU histology)
Patients name
BW
Exclusion criteria
tumor with AFP < 100 ng/ml
tumor with high risk features (V, P, E, M)
Age
Ht
Sex
HN
BSA
Given dose
Drug
Desired dose
Route
Day
___________ mg
Cisplatin (CDDP)
80 mg/m2/dose
IV drip in 24 hr
Give chemotherapy q 2 weeks, ANC > 1,000 and platelet > 100,000 before start chemotherapy
Blood for LFT, AFP before each course and record liver size every course
If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) xBW]
G-CSF is not necessary, unless the patient has febrile neutropenia from the previous course
Initial surgery yes ( Date _____/_____/_____ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other________________________
section # ______________ result ______________________________________________________________
Course
Date
___/___/___
II
___/___/___
III
___/___/___
IV
___/___/___
AFP
Dose adjusted
liver size
Hepatoblastoma: Treatment summary for low risk hepatoblastoma [ThaiPOG-HB-13-LR]
Hearing test
*
252

Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR]
result.
4. If CT chest is not available before the treatment, it MUST be done no later than 14 days after starting of
the first course of chemotherapy
5. Chemotherapy will be given every 2 weeks for 4 courses, then re-evaluate with imaging*
- Resectable tumor surgery plus 2 additional courses of CMT
- Unresectable tumor 2 more courses of CMT, follow with surgery, no post-op CMT
*Imaging is not necessary at this time point for patients with SCU cell type or residual disease from initial
surgery; they will receive chemotherapy for the total of 6 courses
6. Maximum CMT is 6 courses for intermediate risk patient
treatment
1. Ondansetron 5 mg/m2/dose iv pre-chemo and then q 8 hr PLUS
2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) iv drip in 10 min pre-chemo, then q 12 hr
Hepatoblastoma: Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR]
253

Protocol name
Protocol for
Open date
Modified from
ThaiPOG-HB-13-IR
Intermediate risk hepatoblastoma
January 2014
N Engl J Med 2009;361:1662-70
Patient eligibility
Exclusion criteria
PRETEXT I, II, III without upfront surgery
tumor with high risk features (+V, P, E, M)
PRETEXT I, II, III with SCU cell type
AFP < 100 ng/ml
PRETEXT I, II, III with residual disease from upfront surgery
Patients name
BW
Age
Ht
Sex
HN
BSA
Given dose
Drug
Desired dose
Route
Day
___________ mg
Cisplatin (CDDP)
80 mg/m2/dose
IV drip in 24 hr
If BW < 12 kg, calculate chemotherapeutic agent dose per kg [(desired dose/ 30) x BW]
Initial surgery no yes ( Date _____/_____/_____ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other___________________
section # ______________ result ______________________________________________________________
Course
Date
___/___/___
II
___/___/___
III
___/___/___
IV
___/___/___
AFP
Dose adjusted
liver size
Hearing test
*
Re-evaluate after 4 courses of CMT (Date ________________)

Resectable : Surgery plus 2 more courses of CMT
Unresectable : 2 additional courses of CMT, then surgery, no post-op CMT
PRETEXT I, II, III with residual disease or SCU cell type: No imaging needed, continue CMT until
finish cycle 6
V
___/___/___
VI
___/___/___
Delayed surgery ( Date _____/_____/_____ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other_________________________
section # ______________ result ____________________________________________________________________
Hepatoblastoma: Treatment summary for intermediate risk hepatoblastoma [ThaiPOG-HB-13-IR]
254

Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR]
2. If CT chest is not available before the treatment, it SHOULD be done no later than 14 days after starting
of the first course of chemotherapy
3. Chemotherapy will be given every 2 weeks for 7 courses, then re-evaluate
- Resectable tumor will proceed to surgery, then receive 3 additional courses of CMT
- Unresectable tumor will receive 3 more courses of CMT, follow with surgery, no post-op CMT
4. Maximum CMT is 10 courses for high risk patient

treatment
1. Ondansetron 5 mg/m2/dose iv pre-chemo and then q 8 hr PLUS
2. Dexamethasone 8 mg/m2/dose (max 20 mg/dose) iv drip in 10 min pre-chemo, then q 12 hr
Hepatoblastoma: Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR]
255

Protocol name
ThaiPOG-HB-13-HR
Protocol for
Open date
Reference
High risk hepatoblastoma

January 2014
J Clin Oncol 2010;28:2584-2590
Patient eligibility
PRETEXT IV tumor
Tumor with high risk features (+V, P, E, M)
Patients name
BW
Exclusion criteria
Low AFP (< 100 ng/ml)
Age
Ht
Given dose
Drug
Sex
BSA
Desired dose
HN
Day
___________ mg Cisplatin (CDDP)
80 mg/m2 IV drip in 24 hr Day 1 of course 1, 3, 5, 7, 9
___________ mg Carboplatin
500 mg/m2 IV drip in 1 hr Day 1 of course 2, 4, 6, 8, 10
___________ mg Doxorubicin
60 mg/m2 IV drip in 48 hr Day 1-2 of course 2, 4, 6, 8, 10
Initial Biopsy
Course
Date
no
yes
( Date ___/___/___ ) section # ______________ result _________________

AFP
Dose adjusted
liver size
I
___/___/___
II
___/___/___
III
___/___/___
IV
___/___/___
V
___/___/___
VI
___/___/___
VII
___/___/___
Re-evaluate after 7 courses of CMT (Date ________________)
Resectable : Surgery plus 3 more courses of chemotherapy
Unresectable : Give 3 additional courses of CMT, then surgery, no post-op CMT
VIII
___/___/___
IX
___/___/___
X
___/___/___
Hearing test
*
Delayed surgery ( Date ___/___/___ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other_________________
section # ______________ result ____________________________________________________________
Hepatoblastoma: Treatment summary for high risk hepatoblastoma [ThaiPOG-HB-13-HR]
256

Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR]
1. Patients with low AFP (AFP <100 ng/ml) will need biopsy to confirm the diagnosis of hepatoblastoma,
these patients will be classified as a very high risk group
3. If CT chest is not available before the treatment, it SHOULD be done no later than 14 days after starting
of the first course of chemotherapy
4. All patients will receive upfront chemotherapy with 2 courses of VI regimen, then re-evaluate
- Responder will then receive another 9 courses of chemotherapy (C5VD-C5VD-VI x 3 cycles)

: 6 courses of neo-adjuvant CMT followed with Surgery, and 3 course of adjuvant CMT
- Non-responder will receive another 6 course of chemotherapy (C5VD x 6 cycles)
: 4 courses of neo-adjuvant CMT followed with Surgery, and 2 course of adjuvant CMT
5. Surgery will be performed after the 4th course of C5VD regimen of each protocol
treatment
Hepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR]
257

Protocol name
Protocol for
Open date
Reference
ThaiPOG-HB-13-VHR
Very High risk hepatoblastoma
January 2014
COG AHEP0731 protocol, treatment regimen W
Patient eligibility
Patient with low AFP (< 100 ng/ml)
Patients name
BW
Age
Ht
Sex
HN
BSA
Regimen
Given Dose
Drug
Desired dose
Day
VI regimen
____________ mg
Vincristine (VCR)
1.5 mg/m2 IV push
1, 8
____________ mg
Irinotecan
1-5
____________ mg
Cisplatin (CDDP)
____________ mg
5-Flouracil (5-FU)
600 mg/m2 IV push slowly
____________ mg
Vincristine (VCR)
1.5 mg/m2 IV push
2, 9, 16
____________ mg
Doxorubicin
1, 2
C5VD regimen
___________ mg
Ondansetron
5 mg/m2 IV pre-chemo, then q 8 hr during CMT
___________ mg
Dexamethasone*
8 mg/m2 IV drip in 10 min pre-chemo, then q 12 hr during CMT
___________ mg
Aprepitant**
125 mg PO on day 1, then 80 mg PO daily on day 2,3
* Reduce Dexamethasone by half, if Aprepitant was given

**May be given as an additional anti-emetic in patient >12 year
Start G-CSF 5 ug/kg daily at 24-36 hours after completion of each cycle of chemotherapy
Surgery will be performed after the 4th course of C5VD regimen of each protocol
258

Patients name
BW
Age
Ht
Sex
HN
BSA
ThaiPOG-HB-13-VHR protocol
Initial Biopsy no yes ( Date ___/___/___ ) section # ______________
result__________________________
Course
Date
Regimen
___/___/___
VI
II
___/___/___
VI
AFP
Dose adjusted
liver
size
Hearing test
*
Re-evaluate after 2 upfront VI regimen (Date ________________)

Responder
: will receive VI regimen after each 2 cycles of C5VD regimen
Non-responder : will receive 6 additional courses of C5VD (no more VI regimen)
III
___/___/___
C5VD
IV
___/___/___
C5VD
V*
___/___/___
VI*
VI
___/___/___
C5VD
VII
___/___/___
C5VD
VIII*
___/___/___
VI*
Re-evaluate after the 4th course of C5VD regimen (Date ________________)

Resectable : Surgery plus 2-3 more courses of chemotherapy
Unresectable : 2-3 additional courses of CMT then surgery, no post-op CMT
IX
___/___/___
C5VD
___/___/___
C5VD
XI*
___/___/___
VI*
Delayed surgery ( Date ___/___/___ surgeon________________________ )

Operation biopsy partial removal total removal wide excision other___________________
section # ______________ result ____________________________________________________________
*For those who response to upfront VI regimen only (responder)
259

Osteosarcoma
Data entry form
Address....................................................................................................................................................................
..........................................................................Contact person....................................Tel......................................
Fathers name........................................................ Age...........yr Occupation.......................................
Mothers name........................................................ Age...........yr Occupation......................................
Date of Birth (dd/mm/yy)............................................. Date of Diagnosis (dd/mm/yy) ..........................................
Age ............... yr...............m.
BW...............kg
Ht...............cm.
BSA...............m2

() .............................................
History
Primary site Femur

Humerus Tibia Fibula Other bones...
Side
Left
Right
Metastasis site at diagnosis
yes No If yes, specify
Bone Chest Other
Status at first visit (Tumor size cm):
Resectable, non-metastasis Resectable, metastasis
Non-resectable
Histology
Osteoblastic
Telangiectatic
Epithelioid
Chondroblastic
Small cell
Not-classified
Fibroblastic
Large cell
Other..
Surgery
Surgery date (//)
Surgeon ..
Type of surgery: Amputation
Limb salvage
Rotationplasty
.
Tumor necrosis % Pathology ..
Surgical margin Adequate (> 5 cm) Inadequate (not free margin, margin < 5 cm.) not known
Investigations.
serum ALP (//) iu/mL
Normal
Elevated
CT/ MRI primary lesion (//) .......
.
Work up metastasis
CXR Normal
Abnormal
CT chest. Normal
Abnormal
Bone scan.. Normal
Abnormal
Other Normal
Abnormal
Osteosarcoma: Data entry form
260

Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD]
Protocol name ThaiPOG-OS-13-CD
Protocol for High grade localized-osteosarcoma, chondrosarcoma, fibrosarcoma
Reference
SJCRH-OS-99 (launched December 2009)
Open Date
January 2014
Inclusion criteria
Localized osteosarcoma
Cycle
Week
I
Cb
I
Cb
I
Cb
A*
12
10
11
12
14
17
20
23
26
29
32
35
I
A
I
Cb
A
Cb
I
A
I
Cb
A
I A**
Cb A** Cb
38
Date
Induction
Evaluation
(1)
(1)
Surgery
Sx
Hearing test (audiogram) should be evaluated before starting chemotherapy with cisplatin
G-CSF 5 mcg/kg/day is administered for 8 10 days after completion of every cycle except for week 9
Keep ANC 1,500/uL and Platelet count 100,000 /uL before starting chemotherapy
Give chemotherapy every 21 days
(1) Evaluation by CT/MRI lesion, CT chest and CXR PA, lateral
Drug
Dose
Route
2
I: Ifosfamide
2.65 gm/m /day
IV drip in 30 min OD x 3 days
2
Mesna
660 mg/m /dose
IV at 0, 3rd, 6th, 9th hour after Ifosfamide
Cb: Carboplatin
450 mg/m2
IV drip 1 hour OD x 1 day
2
A*: Doxorubicin
25 mg/m
IV drip in 1 hour OD x 3 days
2
A: Doxorubicin
50 mg/m /day
IV drip in 2 hour OD x 1 day
A**: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%)
(Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m2 or when >
200 mg/m2 in infant
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13-CD]
261

Phase I: Neoadjuvant phase
Ifosfamide
Carboplatin
Doxorubicin
Note
Cycle
Date
BSA
2
2
2
2.65 gm/m /day
450 mg/m
25 mg/m
1
2
3
4
Surgery
Surgery date (//)
Surgeon ...
Limb salvage
Rotationplasty
.
Tumor necrosis % Patho no. ..
Surgical margin Adequate (> 5 cm) Inadequate (not free margin, margin < 5 cm.) not known
Evaluation
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
3. CXR/CT scan chest (//) .....
Phase I: Adjuvant phase
Cycle
Date
BSA
Ifosfamide
2.65 gm/m2/day
Carboplatin
450 mg/m2
Doxorubicin
50 mg/m2
Note
5
6
7
8
9
10
11
12
262

Drug administration
A. High dose Ifosfamide (>1,000 mg/m2)
1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m2/hour at least 2 hours before start the
drug, to keep urine output > 3 ml/kg/hour
2. Check urine specific gravity and start chemotherapy when urine specific gravity < 1.010
3. Dilute ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and infuse in 1 hour
4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3 rd, 6th, 9th hour of Ifosfamide; dilute
mesna with 5%D/W to 20 ml iv drip in 15 minute
5. Keep urine output > 2 ml/kg/hour at least 24 hour after high dose Ifosfamide
6. Furosemide 0.5 mg/kg/dose can be used to increase urine volume
B. Carboplatin
1. Dilute carboplatin in 100 mL of 5%D/W infuse intravenously over 1 hour prior to ifosfamide or
doxorubicin on Day 1 of each course
263

Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX]
Protocol name ThaiPOG-OS-13- MTX
Protocol for High grade localized-osteosarcoma, chondrosarcoma, fibrosarcoma
Reference
Adapted from AOST0331 and SSG-XIV (Smeland S. Acta Orthop 2011; 82(2):211-6)
Open Date
January 2014
Inclusion criteria: Localized osteosarcoma
Cycle
Week
Date
Induction
1
2
3
0 3 4 5 8 9 10 13 14
4
5
6
7
15 18 19 20 23 24 25 28 29 30
A
A
A*
M M
M M
M M
P
P
P
Evaluation (1)
(1)
Surgery
Sx
(1)
Adjuvant I
(2)
A
M M A* M M A* M M
P
A
Adjuvant II
M M I M M I M M I
(3)
P
G-CSF 5 mcg/kg/day is administered for 8 10 days after completion of every AP or I cycle
(2) If tumor necrosis > 90%, continue chemotherapy with Adjuvant I
(3) If tumor necrosis < 90 %, continue chemotherapy with Adjuvant II
Drug
Dose
Route
2
A: Doxorubicin 37.5 mg/m /day
IV x 2 days (IV slowly push)
2
P: Cisplatin
60
mg/m /day
IV over 6 hours x 2 days
2
M: HD MTX
12
gm/m /day
IV over 4 hour (max 20 gm)
2
Leucovorin
15
mg/m /dose
IV every 6 h, starting at 24 h after MTX infusion x 11 doses
2
I: Ifosfamide
2.4
gm/m /day
2
Mesna
600 mg/m /dose
IV at 0, 3rd, 6th, 9th hour of Ifosfamide
A*: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%)
(Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m 2 or when
> 200 mg/m2 in infant
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 264

Phase I: Induction phase
Cisplatin
Doxorubicin
HD MTX
Note
Cycle Week
Date
BSA
2
2
2
60 mg/m /day 37.5 mg/m /day 12 gm/m /day
1
0
3
4
2
5
8
9
10
(**)
13
14
Cumulative dose (mg/m2)
Surgery
Surgery date (//)
Surgeon ...
Limb salvage
Rotationplasty
.
Tumor necrosis %
Surgical margin Adequate (> 5 cm) Inadequate (not free margin, margin < 5 cm.)
Evaluation
4. CT/ MRI .(//) .....
5. Bone scan (//) ......

2nd Audiogram (postoperative)
Normal
Sensorineural hearing loss
*Echocardiogram (postoperative)
Normal
Impaired ejection fraction . %
Phase II: Adjuvant I (If tumor necrosis 90%)
Cisplatin
Doxorubicin
MTX
Cycle week
Date
BSA
Note
60 mg/m2/day
15
37.5 mg/m2/day
12 gm/m2/day
(***)
18
19
5
Cumulative dose (mg/m2)

20
(**)
23
24
6
25
(**)
28
29
Phase II: Adjuvant II (tumor necrosis < 90%)
Cycle Week
Date
BSA Cisplatin
60 mg/m2/day
15
Doxorubicin
37.5 mg/m2/day
MTX
12 gm/m2/day
Ifosfamide
2.4 gm/m2/day
Note
(***)
18
19
5
20
23
24
25
28
29
30
7
*Cardiology consultation for 2nd echocardiogram when cumulative dose of doxorubicin was exceeding 325
mg/m2 or 200 mg/m2 in infants
** Doxorubicin can be omitted or reduced when cumulative dose of doxorubicin was exceeding 375 mg/m2 or
impaired cardiac function (ejection fraction < 60%)
*** Cisplatin can be omitted when cumulative dose of cisplatin was exceeding 480 mg/m 2 or evidence of
sensorineural hearing loss

Drug administration
A. High dose methotrexate
Pre- and post-hydration is recommended for high dose methotrexate as follows:
1. Pre Hydration: Start hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20
mL/L at least 24 hours before starting methotrexate infusion, to obtain urine output > 2 ml/kg/h and urinary
pH 7 7.5 (suggested volume 125 ml/m2/hour, could be adjusted as appropriate)
Ensure urine pH is maintained pH 7 7.5 by adjusting sodium bicarbonate if required
Other strengths of dextrose/ saline are acceptable
2. Leucovorin (Calcium folinate) rescue must be commenced exactly 24 hours after the start of the
methotrexate infusion at 15 mg/m2 every 6 hours for 11 doses either intravenously or orally (Folinic acid is
available orally as 15 mg tablets so a dose of 15 mg or 30 mg should be prescribed)
*If serum methotrexate level can be measured, treatment must be continued until methotrexate level
is < 0.1 micromol/L
*Methotrexate levels should be checked every 24 hours commencing at 48 hours from the start of
the methotrexate infusion and continuing until methotrexate level is < 0.1 micromol/L
3. Post hydration: Hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20 mL/L
(alternative strengths accepted) at a rate suitable to obtain urine output > 2 ml/kg/h and urinary pH 7 7.5
(suggested volume 125 ml/m2/h,could be adjusted as appropriate) until methotrexate level < 0.1 micromol/L
If serum methotrexate level is not available,
o Liver function test and serum creatinine must be measured at 72nd and 120th hours after
completion of methotrexate infusion
o If AST / ALT > 5 times of upper normal limits or elevated serum creatinine (>1.5 times of
baseline serum creatinine), folinic acid must be continued up to 7 days
o Hydration (at a rate of 125 ml/m2/hour) should be maintained for at least 7 days
*If MTX level > toxicity alert, increase dose of calcium folinate to (40 x actual MTX conc.) normal MTX conc
(mg/dose)
Time
MTX toxicity alert
Normal MTX conc
Calcium folinate dose
24 h
20 mmol/L
9 mmol/L
As above
48 h
2 mmol/L
0.9 mmol/L
As above
72 h
0.1-0.9 mmol/L
< 0.1 mmol/L
10-30 mg IV every 6h
If MTX level at > 72 h is less than 0.1 mol/L, this patient is allowed to discharge.
B. High dose Ifosfamide (>1,000 mg/m2)
1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m 2/hour at least 2 hours before start the drug, to
keep urine output > 3 ml/kg/h
4. Mesna Uroprotection (total dose = 80% of Ifosfamide) at 0, 3rd, 6th, 9th hour of Ifosfamide; dilute mesna
with 5%D/W to 20 ml iv drip in 15 minute
5. Keep urine output > 2 ml/kg/hour at least 24 hour after high dose cyclophosphamide

Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET]
Protocol name ThaiPOG-OS-13-MET
Protocol for High grade metastatic osteosarcoma
Reference
AOST0331 (EURAMOS01)
Open Date
January 2014
Inclusion criteria
Metastatic osteosarcoma
Week
4 5 6
9 10 11 12 15 16 19 20 23 24 27 28 31 32 35 36 39 40
Date
A M I M A M I M A** M I M A** M M
P
E
I*
E
P
E
I*
Evaluation
(1)
(1)
(1)
Surgery
Sx
G-CSF 5 mcg/kg/day is administered for 8 10 days after completion of every cycle except for week 9
Give chemotherapy every 21 days
Drug
Dose
Route
2
A: Doxorubicin 37.5 mg/m /day
IV x 2 days (IV slowly push)
2
P: Cisplatin
60
mg/m /day
IV over 6 hours x 2 days
2
M: HD MTX
12
gm/m /day
IV over 4 hour (max 20 gm)
2
Leucovorin
15
mg/m /dose IV every 6 h, starting at 24 h after MTX infusion x 11 doses
I: Ifosfamide
2.4
gm/m2/day
2
Mesna
600
mg/m /dose IV at 0, 3rd, 6th, 9th hour after Ifosfamide
I*: Ifosfamide
2.4
gm/m2/day
2
E: Etoposide
100
mg/m /day
A**: Doxorubicin can be omitted or reduced when impaired cardiac function (ejection fraction < 60%)
(Consult cardiologist for Echocardiogram when accumulative dose of doxorubicin > 300 mg/ m 2 or when
> 200 mg/m2 in infant
Induction
A M M A M M
P
P
Osteosarcoma: Treatment protocol for metastatic osteosarcoma [ThaiPOG-OS-13-MET]
268

Phase I: Neoadjuvant phase
Cisplatin
Doxorubicin
HD MTX
Note
Week
Date
BSA
2
2
2
60 mg/m /day 37.5 mg/m /day 12 gm/m /day
1
4
5
6
9
10
Surgery
Surgery date (//)
Surgeon ...
Limb salvage
Rotationplasty
.
Tumor necrosis %
Evaluation
7. CT/ MRI .(//) .....
8. Bone scan (//) ......
Phase I: Adjuvant phase
Cycle
Date
BSA
Cisplatin
2
60 mg/m /day
Doxorubicin
2
37.5 mg/m /day
HD MTX
2
12 gm/m /day
Ifosfamide
2
2.4 gm/m /day
Etoposide
Note
100mg/m /day
12
15
16
19
20
(*)
23
24
Cumulative dose
360
(mg/m2)
2nd Audiogram (postoperative)
*Echocardiogram (postoperative)
300
Normal
Normal

269

Evaluation
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
Cycle
Date
BSA
Cisplatin
Doxorubicin
HD MTX
Ifosfamide
Etoposide
60 mg/m /day
37.5 mg/m /day
12 gm/m /day
2.4 gm/m /day
100mg/m /day
Note
27
28
31
32
35
(*)
36
39
40
3 Audiogram (end of treatment)
* Echocardiogram (end of treatment)
nd
Normal
Normal

*Cardiology consultation for 2nd echocardiogram when cumulative dose of doxorubicin was exceeding 325
mg/m2 or 200 mg/m2 in infants
** Doxorubicin can be omitted or reduced when cumulative dose of doxorubicin was exceeding 375 mg/m 2 or
impaired cardiac function (ejection fraction < 60%)
*** Cisplatin can be omitted when cumulative dose of cisplatin was exceeding 480 mg/m 2 or evidence of
sensorineural hearing loss
270

Drug administration
A. High dose methotrexate
Pre- and post-hydration is recommended for high dose methotrexate as follows:
1. Pre Hydration: Start hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20
mL/L at least 24 hours before starting methotrexate infusion, to obtain urine output > 2 ml/kg/hr and urinary
pH 7 7.5 (suggested volume 125 ml/m2/hour, could be adjusted as appropriate)
Ensure urine pH is maintained pH 7 7.5 by adjusting sodium bicarbonate if required
Other strengths of dextrose/ saline are acceptable
2. Leucovorin (Calcium folinate) rescue must be commenced exactly 24 hours after the start of the
methotrexate infusion at 15 mg/m2 every 6 hours for 11 doses either intravenously or orally (Folinic acid is
available orally as 15 mg tablets so a dose of 15 mg or 30 mg should be prescribed)
*If serum methotrexate level can be measured, treatment must be continued until methotrexate level
is < 0.1 micromol/L
*Methotrexate levels should be checked every 24 hours commencing at 48 hours from the start of
the methotrexate infusion and continuing until methotrexate level is < 0.1 micromol/L
3. Post hydration: Hydration with 5% Dextrose / 0.45% Sodium chloride with sodium bicarbonate 20 mL/L
(alternative strengths accepted) at a rate suitable to obtain urine output > 2 ml/kg/hr and urinary pH 7 7.5
(suggested volume 125 ml/m2/h,could be adjusted as appropriate) until methotrexate level < 0.1 micromol/L
If serum methotrexate level is not available,
o Liver function test and serum creatinine must be measured at 72nd and 120th hours after
completion of methotrexate infusion
o If AST / ALT > 5 times of upper normal limits or elevated serum creatinine (>1.5 times of
baseline serum creatinine), folinic acid must be continued up to 7 days
o Hydration (at a rate of 125 ml/m2/) should be maintained for at least 7 days
*If MTX level > toxicity alert, increase dose of calcium folinate to (40 x actual MTX conc.) normal MTX conc
(mg/dose)
Time
MTX toxicity alert
Normal MTX conc
Calcium folinate dose
24 h
20 mmol/L
9 mmol/L
As above
48 h
2 mmol/L
0.9 mmol/L
As above
72 h
0.1-0.9 mmol/L
< 0.1 mmol/L
10-30 mg IV every 6h
If MTX level at > 72 h is less than 0.1 mol/L, this patient is allowed to discharge.
B. High dose Ifosfamide (>1,000 mg/m2)
1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m 2/hour at least 2 hours before start the drug,
to keep urine output > 3 ml/kg/h
4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3 rd, 6th, 9th hour of Ifosfamide; dilute mesna
with 5%D/W to 20 ml IV drip in 15 minute
5. Keep urine output > 2 ml/kg/h at least 24 hour after high dose Ifosfamide
Furosemide 0.5 mg/kg/dose can be used to increase urine volume
271

Ewing Sarcoma Family of Tumors

Data entry form
Address....................................................................................................................................................................
Age ............... yr...............m.
BW...............kg
Ht...............cm.
BSA...............m2

() .............................................
Diagnosis: ... Staging .
History...
.
....
Physical examination of affected part (specific site eg. Pelvis, scapula; size of tumor)
.................................................................................................................................................................................
.................................................................................................................................................................................
................................................................................................................................................................................
Primary site of tumor
.................................
A. Blood date (//)
CBC ......
BUN/Cr Electrolyte..
LFT..
LDHALP Ca...PO4..Uric acid.
B. Imaging study
Plain film of primary site: date (//) ...
.
CXR (//) ...............................................
CT/ MRI of primary site (//) ...
.
CT chest (//) ............................................
.
Whole body bone scan (99 m)Tc-MDP (//) ...
EKG (//) ....
BMA smear (//) ....
BM Biopsy (//) ....
Ewing Sarcoma Family of Tumors: Data entry form
272

Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR]
Protocol name ThaiPOG-EWS-13-SR
Protocol for localized and metastasis EWS
Reference
Womer RB, West DC, Krailo MD, et al. J Clin Oncol 2012;30:4148-54.
Open Date
January 2014
localized EWS
metastatic EWS
Wk
Cycle
date
BW
HT
BSA
Drug
...../....../........
VDC
...../....../........
IE
...../....../........
VDC
...../....../........
IE
...../....../........
VDC
10
...../....../........
IE
Calculated Dose with BSA

VCR 2 mg/ m = ............................................................mg
CTX 1,200 mg/ m2 = ... mg with Mesna
Doxo 37.5 mg/ m2 /day (x2day) = .................................mg
day1.....................................................................................
day2 ................................................................................
Ifosphamide 1,800 mg/ m2 /day Etoposide 100 mg/ m2/day
(x5day) =..mg (x5day) =..mg
day1.... day1...
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
day1.....................................................................................
day2 ................................................................................
day1.... day1...
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
day1.....................................................................................
day2 ................................................................................
day1.... day1...
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
2
Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR]
273

Wk
12
14
16
18
20
22
24
26
28
Cycle
date
BW
HT
BSA
Drug
Calculated Dose with BSA
Surgery (tumor removal) date of...../....../....... .
Adequate margin ( no need for radiation) Inadequate margin (need radiation at primary site)*
VCR 2 mg/ m2 = ............................................................mg
VDC
With
7
...../....../........
*start
day1.....................................................................................
radiation
day2 ................................................................................
day1.... day1...
8
...../....../........
IE
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
9
...../....../........
VDC
day1.....................................................................................
day2 ................................................................................
day1.... day1...
10
...../....../........
IE
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
11
...../....../........
VC
day1.... day1...
12
...../....../........
IE
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
13
...../....../........
VC
day1.... day1...
14
...../....../........
IE
day2 day2...
day3 day3.......
day4 day4
day5....... day5........
274

Start chemotherapy every 2 wks when ANC> 750 and platelet > 75000 and after 24 hours of G-CSF dose
Total cumulative dose of Doxorubicin is 375 mg/ m 2, consult cardiologist at END of protocol for evaluation cardiac
function
I: Ifosphamide
1,800 mg a day for 5 days each cycle with Mesna (attached guideline for Mesna and
rehydration)
E: Etoposide
100 mg/ m2 a day for 5 days each cycle
V: Vincristine
2 mg/ m2 (maximum dose 2 mg)
D: doxorubicin
37.5 mg/ m2 a day for 2 days each cycle
C: Cyclophosphamide 1,200 mg/ m2 with Mesna (attached guideline for Mesna and rehydration)
Radiation*: Start at week 14 of protocol
Localized disease: No need for localized and adequate surgical margin (more than 2 cm but recommended 5 cm)
BUT Consult radiation oncologist for localized disease WITH inadequate surgical margin
(usually 45-55 Gy with conventional fractionation)
Metastatic disease: Consult radiation for metastatic site
Primary site depend on surgical margin (adequate or inadequate margin)
G-CSF 5 microgram per Kg was given after 12 hours of each course of cycle and was to stop when
ANC> 750 and Platelet > 75,000
Give appropriate anti-emetics drugs
275

Follow up schedule after complete treatment
Date of start of treatment
(//)
Date of end of treatment
(//)
1. Primary site : AP and lateral plain radiographs
Every 3 months x 2 years,
Every 12 months x 5 years
MRI with gadolinium and/or CT with contrast If abnormal imaging or symptoms
2. Chest: CT non-contrast
Every 3-6 months x 2 years,
Every 6-12 months x 3 years,
AP and lateral radiographs Every 12 months x 5 years after last CT
3. Bone metastases site: AP and lateral radiographs
MRI with gadolinium and/or CT with contrast If abnormal imaging or symptoms
Whole body (99 m) Tc-MDP Bone Scan If abnormal imaging or symptoms
AP-anterior posterior; MRI-magnetic resonance imaging; CT-computerized tomography;

99 mTc-MDP-99 m technetium methylene disphosphonate
Ewing Sarcoma Family of Tumors: Follow up schedule after complete treatment
276

Anthracycline record sheet
Diagnosis........................................................ Treatment protocol..........................................................................
Consult cardiologist for 2D-Echocardiogram when accumulative dose of doxorubicin > 300 mg / m2 or
when > 200 mg / m2 in infant
Date of Anthracycline used
Dose
mg
mg/m
Ewing Sarcoma Family of Tumors: Anthracycline record sheet
Cumulative dose
mg
mg/m2
EKG/Echo
277

Guideline for administration of high dose cyclophosphamide/ ifosfamide
High dose Cyclophosphamide (>1,000 mg/m2)
1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m 2/hr at least 2 hours before start the drug
2. Check urine specific gravity and start chemotherapy when urine Sp.Gr. < 1.010
3. Dilute CTX in 5%D/NSS/2 to the final concentration of 10 mg/ml and IV infusion in 1 hr
4. Mesna Uroprotection (total dose = 100% of CTX) at 0, 3, 6, 9 hr of CTX
First dose (25% of CTX): IV drip 15 min before start CTX or drip together with CTX at hr 0
2nd, 3rd dose and 4th dose (25 % of CTX) at hour 3, 6, 9
5. Keep the rate of IV fluid at least 2 x maintenance and urine output > 2 ml/kg/h at least 24 hr after
high dose CTX
6. Furosemide 0.5 mg/kg/dose can be used to increase urine volume.
High dose Ifosfamide (>1,000 mg/m2)
1. Start hydration with 5%D in NSS/2 or NSS/3, rate 125 ml/m 2/h at least 2 hours before start the drug
2. Check urine specific gravity and start chemotherapy when urine Sp.Gr. < 1.010
3. Dilute Ifosfamide in 5%D/NSS/2 to the final concentration of 10 mg/ml and IV infusion in 1 hr
4. Mesna Uroprotection (total dose = 100% of Ifosfamide) at 0, 3, 6, 9 hr of Ifosfamide
First dose IV drip 15 min before start Ifosfamide or drip together with Ifos at hour 0
2nd, 3rd and 4th dose (25% of Ifosfamide) at hour 3, 6, and 9
5. Keep the rate of IV fluid at least 2 x maintenance and urine output > 2 ml/kg/h at least 24 hr after
high dose Ifosfamide
Ewing Sarcoma Family of Tumors: Guideline for administration of high dose cyclophosphamide/
ifosfamide
278

Rhabdomyosarcoma
Data entry form
Address....................................................................................................................................................................
Age ............... yr...............m.
BW...............kg
Ht...............cm.
BSA...............m2

() .............................................
History
Favorable site
Orbit
Head and neck (excluding parameningeal)
Genitourinary (non-bladder/non-prostate)
Unfavorable
Bladder/Prostate
Extremities
Cranial, parameningeal
Others, please specify....
Size of primary tumor
5 cm in diameter
> 5 cm in diameter
Regional nodes involvement N0 (Not clinically involved)
N1 (Clinically involved)
NX (Clinical status unknown)
Metastasis
M0 (no metastasis)
M1 (Distant metastasis), please specify ....
Treatment
Upfront surgery
Upfront chemotherapy
Surgery: date (//)
.
Histology:
Embryonal RMS
Alveolar RMS
Others, specify
Pre- treatment investigations
A. CBC (//)
........
B. Imaging study
CT scan (//) ......
CXR PA/lateral (//) ......
CT chest (//) .....
Bone scan (//) Result positive. negative
Bone marrow (optional) (//)
Primary site:
Rhabdomyosarcoma: Data entry form
279

1 2 3 4
Size
Regional node involvement Metastasis
Any
Any
M0
5 cm
N0 or NX
M0
5 cm
N1
M0
> 5 cm
Any
M0
4
Any
Any
Any
M1
F: Favorable sites- (orbit) (genitourinary tract; )
(head and neck; parameningeal);
U: Unfavorable sites- (bladder) (prostate) (extremities) cranial
parameningeal
Paramenigeal: base of skull, nesopharynx, paranasal sinus, infratemporal pterygopalatine fossa
N0: Not clinically involved; N1: Clinically involved; NX: Clinical status unknown
M0: No metastasis; M1: Distant metastasis
Postoperative Clinical Grouping System (IRS) I II III IV
Group
Extent of disease
A. Localized, completely resected, confined to site of origin
I
B. Localized, completely resected, infiltrated beyond site of origin
A. Localized, grossly resected, microscopic residual
B. Regional disease, involved lymph nodes, completely resected
II
C. Regional disease, involved lymph nodes, grossly resected with
microscopic residual
A. Local or regional grossly visible disease after biopsy only:
III
B. Grossly visible disease after 50% resection of primary tumor
IV
Distant metastasis present at diagnosis
LN: lymph nodes, Maurer HM 1975
Rhabdomyosarcoma Prognostic Risk Group and Treatment Schema
LOW, SUBSET 1 LOW, SUBSET 2
INTERMEDIATE
HIGH
Risk Group Stage*
Group**
Histology
Protocol
1
I-II
Embryonal RMS
LOW1
1
III (Orbit)
Embryonal RMS
Low, subset 1
VAC 4 cycles, then VA 4 cycles
2
I-II
Embryonal RMS
1
III (non-orbit)
Embryonal RMS
LOW2
Low, subset 2
VAC for 45 weeks
3
I-II
Embryonal RMS
2-3
III
Embryonal RMS
INTERMEDIATE
Intermediate
VAC for 39 weeks
1-3
I-III
Alveolar RMS
4
IV
Embryonal RMS
HIGH
High
IVA/CbEV/IVE/VAC
4
IV
Alveolar RMS
A: Dactinomycin; C: Cyclophosphamide; Cb: Carboplatin; E: Etoposide; I: Ifosfamide; V: Vincristine
Malempati S 2012, Breneman JC 2003
Pre-treatment staging (STS-COG)
Stage
Site
1
F
2
U
3
U
Rhabdomyosarcoma: Data entry form
280

First Year after Completion of Therapy
1.
Physical examination including complete blood count every 3 months.
2.
Chest radiograph every 3 months.
3.
Appropriate imaging studies (i.e., CT or MRI of the involved region) every 3-6 months.
4.
Appropriate studies outlined below.
Second and Third Years after Completion of Therapy
1.
Physical examination including complete blood count every 4 months.
2.
Chest radiograph every 4 months.
3.
Appropriate imaging studies every 4-6 months.
Fourth Year
1.
Above studies every 6-12 months.
Fifth to Tenth Years after Completion of Therapy
1.
Annual visit for physical examination and studies outlined below.
2.
Referral to a survivorship program strongly recommended.
Ten Years after Completion of Therapy
1.
Maintain yearly visit or phone contact.
2.
Record attainment of puberty and pregnancy.
3.
Long-term follow-up in a survivorship program strongly recommended.
Rhabdomyosarcoma: Post-treatment evaluation
281

Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1]
Cycle
Week
Chemo
1
2
3
4
1 2 3 4 5 6 7 8 9 10 11 12
V V V V V V V V V V V V
A
A
A
A
C
C
C
C
Evaluation
Protocol name ThaiPOG-RMS-13-LR1

Protocol for
Low risk, subset 1, rhabdomyosarcoma
Reference
Walterhouse D et al. JCO 2011
Open date
January 2014
Inclusion criteria
Embryonal rhabdomyosarcoma, stage 1 group I/II or III (orbit) M0
Embryonal rhabdomyosarcoma, stage 2 group I/II M0
5
6
7
8
13 14 15 16 17 18 19 20 21 22
V V V V V V V V V V
A
A
A
A
-
Surgery +Radiotherapy*
*Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes
who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week
13
**Dactinomycin is omitted during radiotherapy
Drug
V: Vincristine
A: Dactinomycin*
C: Cyclophosphamide
Dosage
1.5 mg/m2 /day IV push slowly (maximum dose, 2 mg)
0.045 mg/kg/day IV push slowly (maximum dose, 2 mg)
1.2 gm/m2/dose IV drip in 1 hr x 1 day
Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR1]
Total dose
282

Vincristine
Dactinomycin
Cyclophosphamide
Note
Cycle
Date
BSA
2
2
(1.5 mg/m /dose) (0.045 mg/kg/day)
(1.2 gm/m )
1
2
3
4
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Radiotherapy date (//) Total dose (Gy): .
Technique: .. Involved field: .
- Embryonal rhabdomyosarcoma group I:
- Embryonal rhabdomyosarcoma group II, node negative: 36 Gy
- Embryonal rhabdomyosarcoma group II, node positive: 41.4 Gy
- Embryonal rhabdomyosarcoma group III (orbit only): 45 Gy
RMS group III
(node negative) 13 13
13 dactinomycin
Evaluation
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
2
(1.5 mg/m /dose) (0.045 mg/kg/day)
(1.2 gm/m2)
Note
5
6
7
8
283

Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-LR2]
Protocol name ThaiPOG-RMS-13-LR2
Protocol for
Low risk, subset 2, rhabdomyosarcoma
Reference
Raney RB et al. JCO 2011;29:1312-8
Open date
January 2014
Inclusion criteria
Embryonal rhabdomyosarcoma, stage 1 group III (non-orbit) M0
Embryonal rhabdomyosarcoma, stage 3 group I/II M0
Cycle
Week
Chemo
1
2
3
4
5
6
7
8
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
V V V V V V V V V - - - V V V V V V V V V - - A
A
A*
A
A
A*
A*
A
C
C
C
C
C
C
C
Radiotherapy
(group II or III)
Radiotherapy
(if indicated)
Cycle
Week
Chemo
9
10
11
12
13
14
15
16
24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
V V V V V V V V V - - - V V V V V V V V V A
A
A*
A*
A
A
A
A
C
C
C
C
C
C
Radiotherapy
(if indicated)
*Omit dactinomycin at week 6 in patients beginning RT at week 3, weeks 15 and 18 in patients beginning RT at
week 12, and weeks 30 and 33 in patients beginning RT at week 28
Patients with vaginal primaries and tumor-involved regional lymph nodes or with non-orbital, stage 1, group III
tumors start RT at week 12. Patients with vaginal primaries and negative nodes start RT at week 28, if repeat
biopsies show persistent viable tumor cells.
Drug
Age(yrs) Dosage
Total dose
V: Vincristine
<1
0.025 mg/kg IV push slowly (maximum dose, 2 mg) x 1 day
1-3
>3
1.5 mg/m2/day IV push slowly (maximum dose, 2.5 mg) x 1 day
A: Dactinomycin*
<1
0.025 mg/kg x 1 day
1
0.045 mg/kg x 1 day
C:
<1
36 mg/kg IV drip in 1 hr x 1 day
Cyclophosphamide 1-3
(given with mesna) > 3
Mesna
550 mg/m2/dose IV slowly push slowly at 0, 3, 6, 9 hr after
cyclophosphamide infusion
284

Note
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
1
2
3
*
Radiotherapy or Delayed surgery
4
5
6
**
**
8
*Omit dactinomycin at week 6 in patients beginning RT at week 3,
**Omit dactinomycin at weeks 15 and 18 in patients beginning RT at week 12
Patients with vaginal primaries and tumor-involved regional lymph nodes or with non-orbital, stage 1, group III
tumors start RT at week 12.
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Radiotherapy date (//)
Technique: ..
Total dose (Gy): .

Involved field: .
Evaluation
4. CT/ MRI .(//) .....
5. Bone scan (//) ......
285

Note
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
9
10
11
12
13
14
15
16
*Omit dactinomycin at weeks 30 and 33 in patients beginning RT at week 28
Patients with vaginal primaries and negative nodes start RT at week 28, if repeat biopsies show persistent
viable tumor cells.
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Radiotherapy date (//) Total dose (Gy): .
Technique: .. Involved field: .
- Embryonal RMS group I:
- Embryonal RMS group II, node negative: 36 Gy
- Embryonal RMS group II, node positive: 41.4 Gy
- Embryonal RMS group III (non-orbit): 50.4 Gy
residual microscopic/gross residual (group II III) embryonal RMS 3
- RMS vulva, uterus, biliary tract superficial non-parameningeal head/neck (nonorbital stage 1, group III) 12 (delayed primary excision)
- RMS 12
- RMS 28
28
Evaluation
1. CT/ MRI . (//) ....
2. Bone scan (//) ......
286

Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-SR]
Protocol name ThaiPOG-RMS-13-SR
Protocol for
Intermediate risk, rhabdomyosarcoma
Reference
Arndt C A et al. JCO 2009;27:5182-5188
Open date
January 2014
Inclusion criteria
Embryonal rhabdomyosarcoma, stage 2/3 group III, M0
Alveolar rhabdomyosarcoma, non-metastatic disease
Cycle
1
2
3
4
5
6
7
8
Week
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
Chemo V V V V V V V V V V V V V - - V - - V V V V V V
A
A
A
A
A
A
C
C
C
C
C
C
C
C
E* Surgery + Radiotherapy
Cycle
9
10
11
12
13
14
Week
24+ 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Chemo
V - - V - - V - - V V V V - - V - - A
A
A
A
A
A
C
C
C
C
C
C
E**
E
E: evaluation of disease at week 12, 24 and the end of treatment
*In group III patients, excision of the tumor with negative margins should be considered and the radiation dose
was adjusted according to the amount of residual
**Selected patients who responded poorly to induction chemotherapy were recommended to proceed to
preoperative RT followed by second-look surgery at week 24
RT began 2 to 3 days after completion of week 12 chemotherapy if no biopsy or second-look operation was
done, or 2 to 3 weeks after surgery for patients who underwent second-look surgery
Drug
Age(yrs) Dosage
Total dose
V: Vincristine
<1
1-3
>3
1.5 mg/m2/day IV push slowly (maximum dose, 2.5 mg) x 1 day
A: Dactinomycin*
<1
0.025 mg/kg x 1 day
1
0.045 mg/kg x 1 day
C:
<1
Cyclophosphamide 1-3
(given with mesna) > 3
Mesna
550 mg/m2/dose IV slowly push slowly at 0, 3, 6, 9 hr after
cyclophosphamide infusion
Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-SR]
287

Note
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
1
RADIOTHERAPY (parameningeal RMS with intracranial extension)* __________________
2
3
4
5
**
Re-evaluation and Radiotherapy or Delayed surgery
7
8
* parameningeal RMS intracranial extension (
dura mater ) VAC
(immediate radiotherapy) 1 VAC
**Vincristine is given only on day 1 (omit on day 8, 15)
group III 12
(margin negative) 12 (second-look surgery)
2-3
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Total dose (Gy): .
Technique: ..
Involved field: .
- Embryonal/Alveolar RMS group IV: RT 50.4 Gy
- Embryonal/Alveolar RMS group IV, second look surgery, margin negative: RT 36 Gy
- Embryonal/Alveolar RMS group IV, second look surgery, margin negative: RT 41.4 Gy
Evaluation
7. CT/ MRI .(//) .....
8. Bone scan (//) ......
288

Note
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
9
*
Re-evaluation** and Radiotherapy or Delayed surgery
10
11
12
13
14
*
Re-evaluation
*Vincristine is given only on day 1 (omit on day 8, 15)

**Selected patients who responded poorly to induction chemotherapy were recommended to proceed to
preoperative RT followed by second-look surgery at week 24
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Total dose (Gy): .
Technique: ..
Involved field: .
Evaluation
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
289

Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-HR]
Protocol name ThaiPOG-RMS-13-HR
Protocol for
High risk, rhabdomyosarcoma
Reference
Oberlin O et al. JCO 2012;30:2457-65
Open date
January 2014
Inclusion criteria
Metastatic disease
Phase I: Induction Phase
Cycle 1
2
3
4
5
6
7
8
9
Week 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
Chemo I V V Cb V V I
I
Cb
I
I
Cb
I
V
E
V
V
E
V
V
E
V
A
V
E
A
V
E
A
V
E
E*
E*
E*
Radiotherapy**
Re-surgery or
Radiotherapy
Phase II: Maintenance Phase
Cycle 10
11
12
13
14
15
16
17
18
Week 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52
Chemo V
V
V
V
V
V
V
V
V
A
A
A
A
A
A
A
A
A
C
C
C
C
C
C
C
C
C
E*
E*
For children less than 1 year of age or weighing less than 10 kg, the full combination of drugs are introduced at
66% of the calculated meter-squared dose and increased gradually toward the full meter-squared dose for
subsequent courses of treatment as tolerated.
*E: evaluation
**Radiation to all patients age 3 years with parameningeal disease and to all patients who achieved partial
response < 50%
Radiation to all patients who not received radiation at 9th week of chemotherapy
Drug
Dosage
Total dose
2
I: Ifosfamide
3.0 gm/m /dose IV drip in 1 hr x 3 days
Mesna
600 mg/m2/dose IV slowly push slowly at 0, 3, 6, 9, 12 hr after
ifosfamide infusion
V: Vincristine
1.5 mg/m2/day IV push slowly (maxinum dose, 2 mg) x 1 day
A: Dactinomycin*
1.5 mg/m2/day IV push slowly (maxinum dose, 2 mg) x 1 day
Cb: Carboplatin
500 mg/m2/day IV drip in 1 hr x 1 day
E: Etoposide
150 mg/m2/day IV drip in 2 hr x 1 day
C: Cyclophosphamide 1.0 gm/m2/dose IV drip in 1 hr x 1 day
Rhabdomyosarcoma: Treatment protocol for rhabdomyosarcoma [ThaiPOG-RMS-13-HR]
290

Phase I: Induction Phase
Cycle
Date
BSA Ifosfamide Vincristine Dactinomycin Carboplatin Etoposide
Note
1
2
3
*
Evaluation (1) and Radiotherapy**
*
Evaluation (2), Delayed surgery and/or Radiotherapy
Evaluation (3)
*Vincristine is given only on day 1 (omit on day 8, 15)
**Radiation to all patients age 3 years with parameningeal disease and to all patients who achieved partial
response < 50%
Radiation to all patients who not received radiation at 9th week of chemotherapy
Evaluation (1)
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
Radiotherapy
Total dose (Gy): .
Technique: ..
Involved field: .
291

Evaluation (2)
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
Surgery
Surgery date (//)
Surgeon ...
Type of surgery: ..
Radiotherapy
Total dose (Gy): .
Technique: ..
Involved field: .
- Embryonal/Alveolar RMS group IV, second-look surgery, margin negative: RT 36 Gy
- Embryonal/Alveolar RMS group IV, second-look surgery, margin negative: RT 41.4 Gy
Evaluation (3)
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
Phase II: Maintenance Phase
Cycle
Date
BSA
Vincristine
Dactinomycin
Cyclophosphamide
Note
1
2
3
4
5
6
7
8
9
292

Germ Cell Tumor

Staging of germ cell tumor (gonadal and extragonadal)
Germ Cell Tumor: Staging of germ cell tumor (gonadal and extragonadal)
293

gonadal and extragonadal germ cell tumor
Patients suspect germ cell tumor (GCT)
Tumor marker evaluation (-HCG, AFP)
Diagnostic surgery (if possible)
Pathology confirm diagnosis
Mature and
immature teratoma
at any sites
Observation and
monitoring
Low risk
GCT
Intermediate risk
GCT
Observation and
monitoring
High risk*
GCT
Standard PEB regimen

4 courses
Evaluation
Complete
response
Partial
response
Off
treatment
Second
look surgery
Pathology positive for
malignant GCT
Pathology negative
for malignant GCT
Standard PEB regimen

2 courses and follow up
Off
treatment
Germ Cell Tumor: gonadal and extragonadal germ cell tumor
294

Type of germ cell tumor by staging and by risk group
Staging
Staging 1
Staging 2
Staging 3
Staging 4
Ovarian
Low
Intermediate
Intermediate
Intermediate
Testicular
Low
Intermediate
Intermediate
Intermediate
Extragonadal
Intermediate
Intermediate
High
High
germ cell tumor histology staging

Histology
Mature teratoma
Immature teratoma*
Primary site
All sites
All sites
Testicular
Malignant germ cell

tumor and germinoma
Ovary
Extragonadal
Stage
Localized
Localized
Stage 1
Stage 2-4
Stage 1**
Stage 2-4
Stage 1-2
Stage 3-4
Treatment
Surgery +observation
Surgery+ standard PEB
* Immature teratoma rupture cyst PEB

Immature teratoma grade III sacrococcygeal PEB
** Malignant GCT ovary stage I PEB
recurrence
PEB JEB
Regimen
Bleomycin
Etoposide
Cisplatin
2
2
Standard-PEB
15 units/m ,
100 mg/ m ,
20 mg/ m2,
(every 21days)
day 1
day 1-5
day 1-5
2
2
JEB
15 units/m ,
120 mg/ m ,
(every 21-28 days)*
day 1
day 1-3
* JEB PEB cisplatinum
Germ Cell Tumor: Type of germ cell tumor by staging and by risk group
Carboplatin
600 mg/ m2,

day 2
295

Data entry form
Address....................................................................................................................................................................
Age ............... yr...............m.
BW...............kg
Ht...............cm.
BSA...............m2

() .............................................
History
Primary Site and Size
Metastatic Site

A. Blood date (//)
CBC .. -hCG .... AFP....
B. Imaging study
CT chest (//) .....
Chest X-Ray (//) .........
MRI/CT primary lesion (//) .....
Bone scan (in high risk only) (//) .........
Bone marrow aspiration (abnormal CBC only) (//).......
D. Other
Other (//) ...
Initial surgery (//) surgeon........
section # .. result .
Histology ...
Diagnosis Stage
Germ Cell Tumor: Data entry form
296

Treatment protocol for germ cell tumor [ThaiPOG-GCT-13]
Protocol name
Protocol for
Reference
ThaiPOG-GCT-13
Germ Cell Tumor
Cushing B, Giller R, Cullen JW, et al. J Clin Oncol 2004;22(13):2691-700.
Mann JR, Raafat F, Robinson K, et al. J Clin Oncol 2000; 18(22):3809-18.
Open Date
January 2014
Inclusion criteria: Extracranial Germ cell tumor
PEB regimen
Given dose/day
JEB regimen
Given dose/day
Drug
Cisplatin
Etoposide
Bleomycin
Dosage
20 mg/m2IV Day 1-5
100 mg/m2 IV on Day 1-5
15 unit/m2 IV on Days 1
Drug
Carboplatin
Etoposide
Bleomycin
Dosage
600 mg/m2IV Day 2
120 mg/m2 IV on Day 1-3
15 unit/m2 IV on Days 1
Repeat chemotherapy q 3 weeks x 4 courses

ANC > 1,000 and platelet count > 100,000 before start chemotherapy
Blood for LFT, AFP and/or HCG before start chemotherapy
BW < 12 kg, calculate chemotherapeutic agent dose per kg
Standard-PEB
Date
AFP
-hCG
Hearing
Remarks
I
II
III
IV
surgery
V
VI
G-CSF 5 g / kg SC OD Start Day 7 febrile neutropenia
Germ Cell Tumor: Treatment protocol for germ cell tumor [ThaiPOG-GCT-13]
297

cisplatinum (CDDP)
1. CDDP
electrolytes, Ca, Mg, BUN creatinine, U/A
GFR GFR ml/ min/ 1.73 sqm
0.55 x Ht cm
Scr mg/ dL
GFR > 25 ml /min /1.73 sqm

2. 4 .
Hydration 5%D NSS/
(Vol .ml/bottle)
+ KCl (10 mEq/L)
ml + MgSO4 (8 mEq/L) .ml
IV drip at rate
/hr (125 ml/m2/hr) x 4 hr
Hour 0 record I/O 4-6 .
5%D NSS/
Vol .ml
2
+ CDDP
mg (20 mg/m )
+ mannitol
gm (500 mg/kg)
+ KCl
ml (1 mEq/kg)
IV at rate
ml /hr (150 ml/m2/h) x 6 hr
( CDDP 3-4 ml/kg/hr
mannitol 200 mg/kg in 25 ml NSS IV over 15 min
1 . lasix 0.5 mg/kg )
Hour 24 CDDP IV fluid
5%D NSS/
(Vol .ml/bottle)
+ KCl (10 mEq/L)
ml + MgSO4 (8 mEq/L) .ml
IV drip at rate
/hr (125 ml/m2/h) x 18 hr
rate IV ml /hr (65 ml/m2/h)
3. Oral Mg supplement: Minimal daily requirement = 0.3 mEq/kg/d (12 mg Mg = 1 mEq)
Mag oral tab
= 7 mEq Mg/tab
Milk of Magnesia
= 13 mEq Mg/ 5 ml
Mg sulfate solution 50%
= 20 mEq/ 5 ml
Tumor marker: AFP and / or HCG 1-2 6 3

CT or MRI tumor primary site 4 6
cisplatin 4-6
Germ Cell Tumor: cisplatinum (CDDP)
298

Histiocytosis
Langerhans cell histiocytosis
Disease stratification
Low Risk group
-Single or Multiple organ involvement, but WITHOUT involvement of Risk organs
High Risk group
-Multisystem patients with involvement of one or more Risk organs i.e. hematopoietic system, liver,
spleen
Definition of organ involvement
RISK Organs
Hematopoietic involvement (With or
without bone marrow involvement)
Spleen involvement
Liver involvement
Definitions
Anemia (exclusion of iron deficiency)
-Hb < 10 g/dl
-infants, Hb < 9 g/dl
Leukocytopenia
-WBC < 4,000 /mm3
Thrombocytopenia
-platelets < 100,000 /mm3
enlargement > 2 cm below costal margin (proven by sonography)
-enlargement > 3 cm below costal margin (proven by
sonography) and/or
-liver dysfunction (hyperbilirubinemia, hypoproteinemia,
hypalbuminemia, elevated GT, alkaline phosphatase,
elevated transaminases, ascites, edema) and/or
-histopathological diagnosis
Histiocytosis: Langerhans cell histiocytosis
299

LCH treatment guideline
Induction-I
GR
PD
PR/NR
Off protocol
Paliative vs HSCT
Induction-II
GR/PR
Continuation
NR/PD
GR/PR
NR/PD
Salvage
Definition of clinical response

Good Response (GR)
Resolution of all signs or symptoms
Partial Response (PR)
Regression of sign or symptoms, no new lesions
Not Resposponse (NR)
Persistence of signs or symptoms, no new lesions
Progressive Disease (PD)
Progression of signs or Symptoms and/or appearance of new lesions
Note:
Lytic bone lesions can take months to year for resolution. Stable or any resolution of lytic bone lesion is
considered Good Response (GR)
Start PCP prophylaxis as soon as possible and continue until 6 months after end of therapy
Histiocytosis: LCH treatment guideline
300

Data entry form
Patients name
Address
BW
Age
Contact Person
cm BSA
kg Ht
History
Age
Fever
Recurrent infection
Weight loss
Large abdomen
Mass
Bone pain
Rash
Dyspnea/Tachypnea
Polyurea
Other
>2yr
no
no
no
no
no
no
no
no
no
no
<2yr.
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Sex
HN
Tel:
PE
Exopthalmos
Dental anomalies
Otitis media
Lymphadenopathy
Hepatomegaly
Splenomegaly
Skin lesion
Abnormal mass
Growth retardation
Delayed sexual maturation
Other
m2
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
yes
Investigation
CBC: Hb _____ g/dl, Hct ______ %, WBC __________ /mm3, Platelet ____________ / mm3
LFT _________________________________________________________________________________
Coagulogram: PT _____________ sec., aPTT _____________ sec., Fibrinogen ____________
Bone marrow
abnormal normal
Endocrine work up
Diabetes insipidus
yes
no
Other endocrine disorders yes
no specified: __________________________
CXR
positive negative
Bone survey
positive negative
Optional:
Bone scan
positive negative
Lung function test abnormal normal
CT/MRI brain
abnormal normal
Surgery & Pathology
Surgery
Date ___/___/___ surgeon________________________
Operation biopsy curette partial removal total removal wide excision
other_____________________________________________________
Pathology
section # ______________ result ________________________________
Histology ___________________________________________________
Histiocytosis: Data entry form
301

Patients name
Address
BW
kg Ht
Age
Contact Person
cm BSA
Sex
HN
Tel:
m2
Final diagnosis ____________________________________________________

Risk Group _______________________________________________________
Indication for systemic chemotherapy for LCH
1. Low risk LCH (Single-system or multisystem)
Skull lesions in mastoid, temporal, or orbital bones (CNS-risk lesion)

Vertebral or femoral bone lesions (lesion at risk for collapse)
Multiple bone lesions
Combinations of skin or lymph node or pituitary gland with or without bone lesions
2. High risk multisystem LCH
Spleen involvement may or may not include skin, bone, lymph node, lung or pituitary gland
Liver involvement may or may not include skin, bone, lymph node, lung or pituitary gland
Hematologic involvement may or may not include skin, bone, lymph node, lung or pituitary
gland
302

Treatment protocol for Langerhan cell histiocytosis
Reference
Open date
Patients name
Diagnosis
BW
Treatment protocol for low risk LCH; from LCH III study protocol
January 2014
Age
Sex
HN
kg Ht
m2
cm BSA
Phase I INDUCTION
Date Start ___________________
Week
Day
Date given
Prednisolone __________
Vinblastine ____________ mg
1
1
2
8
3
15
4
22
5
29
6
36
taper off
Drug
Dosage
Prednisolone
Vinblastine
40 mg/m /day oral bid-qid then taper off in 2 wk

6 mg/m2 IV push (max 10 mg)
Schedule
Day 1-28
Day 1, 8, 15, 22, 29, 36
Modify dose in infant with BW < 10 kg

Age < 6 months give 50% dosage calculated from BSA
Age 6-12 months give 75% dosage calculated from BSA
Evaluation after week 6 of treatment
imaging of primary lesion ____________________________________________
imaging of metastasis sites ___________________________________________
Bone survey ________________________________________________________
BMA/biopsy or clotted marrow __________________________________________
GR Proceed to continuation therapy
PR/NR and all High risk patient Go on phase II (induction II)
PD Consider salvage regimen
Histiocytosis: Treatment protocol for Langerhan cell histiocytosis
303

Patients name
BW
kg Ht
Phase II INDUCTION II
(For PR/NR and all high risk patients)
Week
Day
Date given
Prednisolone __________
Vinblastine ____________ mg
Age
HN
cm BSA
Date Start ___________________
m2
1
1
2
8
3
15
4
22
5
29
6
36
III
III
III
III
III
III
Drug
Dosage
Prednisolone
Vinblastine
40 mg/m /day oral bid-qid

6 mg/m2 IV push (max 10 mg)
Schedule
Day 1-3 weekly
Day 1, 8, 15, 22, 29, 36
Evaluation after week 6 of treatment

imaging of primary lesion ____________________________________________
imaging of metastasis sites ___________________________________________
Bone survey ________________________________________________________
BMA/biopsy or clotted marrow __________________________________________
GR and PR Proceed to phase III (Continuation treatment)
NR and PD Consider salvage regimen
304

Patients name
Age
HN
BW
kg Ht
cm BSA
Phase III Continuation treatment
Date Start Regimen ________________ / Date Start Maintenance__________________
End of therapy date _______________
m2
Drug
Dose
Pulse Treatment every 3 week
______________ -Vinblastine
6 mg /m2 IV push (max 10 mg) 1
______________ -Prednisolone (5 mg)
40 mg /m2 /day PO
1-5
Maintenance Therapy
______________ -6-MP (50 mg)
50 mg /m2/dose PO hs, daily daily
Total duration of treatment 12 months including induction phase
Continue PCP prophylaxis throughout treatment period and 6 months off therapy
Lab each visit: CBC, BUN, Cr, AST, ALT, Bili, Elyte, ESR
Lab every other visit: UA, Urine osmol
Cycle
Date
Note
BSA:_______VBL: _______Pred: _______6-MP: _______
Cycle
Note
BSA:_______VBL: _______Pred: _______6-MP: _______
11
BSA:_______VBL: _______Pred: _______6-MP: _______
BSA:_______VBL: _______Pred: _______6-MP: _______

12
BSA:_______VBL: _______Pred: _______6-MP: _______

3
BSA:_______VBL: _______Pred: _______6-MP: _______

13
BSA:_______VBL: _______Pred: _______6-MP: _______

4
BSA:_______VBL: _______Pred: _______6-MP: _______

14
BSA:_______VBL: _______Pred: _______6-MP: _______

5
BSA:_______VBL: _______Pred: _______6-MP: _______

15
BSA:_______VBL: _______Pred: _______6-MP: _______

6
BSA:_______VBL: _______Pred: _______6-MP: _______

16
BSA:_______VBL: _______Pred: _______6-MP: _______

7
BSA:_______VBL: _______Pred: _______6-MP: _______

17
BSA:_______VBL: _______Pred: _______6-MP: _______

8
BSA:_______VBL: _______Pred: _______6-MP: _______

18
BSA:_______VBL: _______Pred: _______6-MP: _______

9
BSA:_______VBL: _______Pred: _______6-MP: _______

19
BSA:_______VBL: _______Pred: _______6-MP: _______

10
Date
BSA:_______VBL: _______Pred: _______6-MP: _______

20
305

Patients name
BW
Phase IV
kg Ht
Salvage Regimen
Age
cm BSA
HN
m2
Date Start ___________________
(For patient with progressive disease)

Reference: Apollonsky et al, J Pediatri Hemato Oncol, Vol 31, Jan 2009
Course
Date
Note
1
2
Ara-C ______ mg
Ara-C ______ mg
Ara-C ______ mg
4
*Repeat every 3-4 weeks
Drug
Ara-C
G-CSF
Decadron eye drop
Ara-C ______ mg
Dosage
1,000 mg/m2/day IV over 2 hours
5 mcg/kg SQ/IV daily
1 drop both eyes BID
Schedule
Day 1-5
Day 6 until ANC > 1,000 x 2 days
Day 1-6
Evaluation after cycle 2 and 4 of treatment

imaging of primary lesion
_________________________________________________________________
imaging of metastasis sites
_________________________________________________________________
Bone survey
_________________________________________________________________
BMA/ biopsy + clotted marrow
_________________________________________________________________
GR after cycle 2 Proceed to phase III (Continuation treatment)
PR/NR after cycle 2 Give 2 more cycle of High dose Ara-C
GR/PR after cycle 4 Proceed to phase III (Continuation treatment)
Note:
PD at any point in salvage regimen Off protocol

For patient with only progressive osteolytic lesion consider
-Low dose ARA-C (100 mg/m2) x 5 days for 2-4 cycle
or
-Bisphosphonate 200mg/m2/day PO daily for 14 days Q 3 months
306

Hemophagocytic lymphohistiocytosis
Data entry form
Patients name
Age
Sex
HN
Address
Contact Person
BW
kg Ht
cm BSA
m2
History
Fever
Bleeding
Abdominal mass
CNS symptoms
Other specified:.
Anemia
Physical Examination
Fever
Hepatomegaly
Lymphadenopathy
Anemia
CNS abnormalities
Bleeding evidences
Other specified:.
Splenomegaly
Investigations
CBC (___/___/___) Hct _____% Hb _____g/dL, MCV _____fl, MCHC _____g/dl, Plt ____________/mm3,
WBC ________/mm3 (N ____, L ____, Mo ____, Eo ____, Ba ____, blast ____), Retic count _____%
Viral study HIV
neg pos, Hepatitis profile ___________________________________
CMV
neg pos, EBV neg pos
Other culture: neg pos; specified: _________________________________________
Cancer:
No Yes; specified: _________________________________________
Collagen profile:
neg pos; specified: _________________________________________
Blood Chemistry (___/___/___)
Fibrinogen ______________, Coagulogram : PT ________________ , APTT __________________
LFT ______________________________________________________ , Triglyceride ___________
Ferritin _________________, LDH ___________________, Uric acid ________________________
Immunoglobulin level (___/___/___) : IgG ___________, IgA ___________ , IgM ____________
Molecular study: HLH gene mutation: __________________NK cell acitivity:________________________
BM aspiration (___/___/___) ______________________________________________________________
CXR (___/___/___) _____________________________________________________________________
CSF profile (___/___/___) ________________________________________________________________
MRI/CT primary lesion _____________________ Ultra sound/CT abdomen _____________________
Histiocytosis: Hemophagocytic lymphohistiocytosis
307

Patients name
BW
Age
kg Ht
Sex
cm BSA
HN
m2
Patients eligibility
Familial Hemophagocytic Lymphohistiocytosis
Infectious-associated hemophagocytosis (IAHS)
Malignant-associated hemophagocytosis (MAHS)
Macrophage Activation Syndrome (MAS) refractory to steroid
The diagnosis HLH can be established if one of either 1 or 2 below is fufilled
(1) A molecular diagnosis consistent with HLH
(2) Diagnostic criteria for HLH fulflled (five out of the eight criteria below)
(A) Initial diagnostic criteria (to be evaluated in all patients with HLH)
Fever
Splenomegaly
Cytopenias (affecting 2 of 3 lineages in the peripheral blood)
Hemoglobin < 9 g/L (in infants <4 wks, Hb <10 g/L)
Platelets < 100,000
ANC < 1,000
Hypertriglyceridemia and/or hypofibrinogenemia
Fasting triglycerides 300 mg/dl)
Fibrinogen 150
Hemophagocytosis in bone marrow or spleen or lymph nodes
No evidence of malignancy
(B) New diagnostic criteria
Low or absent NK-cell activity
Ferritin 500 mg/L
Soluble CD25 (i.e., soluble IL-2 receptor) 2,400 U/ml
308

Treatment protocol for hemophagocytic lymphohistiocytosis
Protocol for
Modified from
Open date
Hemophagocytic lymphohistiocytosis
Hemophagocytic lymphohistiocytosis study group 2004
January 2014
Patients name
Age
BW
kg Ht
Sex
Etoposide ________mg*
m2
cm BSA
Phase I Initial therapy (Week 1-8)

Week
Day
HN
Date start ______/______/______
1
1
2
8
3
15
4
22
5
29
6
36
7
43
8
50
10 mg/m2
Dexa ________ mg
5 mg/m2
IVIG ____________ mg
2.5 mg/m2
1.25mg/m2 taper off
CSA________ml** q12hr ____ ml ____ ml ____ ml ____ ml ___ ml ____ ml ____ ml ____ ml
IT#
T#
T#
T#
T#
Drug
Etoposide*
Dosage
Twice weekly for first 2 weeks, then weekly
Schedule
1, 4, 8, 11, 15, 22, 29, 36, 43, 50
Dexamethasone
10 mg/m2/day for 2 weeks
1-14
5 mg/m2/day for 2 weeks
15-28
2.5 mg/m2/day for 2 weeks
29-42
1.25 mg/m2/day for 2 weeks then taper off
43-56
Cyclosporine**
3-5 mg/kg/day q 12hr IV or

6-10 mg/kg/day q 12hr orally
daily
IVIG (for IAHS only)
0.5 g /kg/dose q 4 wk
1, 29, 57
*The first two doses may be omitted if ANC < 500/ mm 3 AND hypocellular marrow
**Keep trough level 150-200 ng/ml
#
Given IT chemotherapy if progressive neurological symptom or abnormal cell persist in CSF only
#
age adjusted dose intrathecal chemotherapy
<1 yr
1-2 yr
2-3 yr
>3 yr
Methotrexate
10
12
Hydrocortisone
10
Histiocytosis: Treatment protocol for hemophagocytic lymphohistiocytosis
309

Patients name
Age
BW
kg Ht
Sex
m2
cm BSA
Phase II Continuation therapy (Week 9-40)

Given dose
HN
Date start ____/____/____
Drug
Dosage
Day
___________ mg
Etoposide
150 mg/m2 IV every 2 weeks
___________ mg
Dexamethasone
10 mg/m2 day PO x 3 days every 2 weeks
8-10
___________ mg
Cyclosporin A
6-10 mg/kg /day PO q 12hr
daily
___________ mg
Cotrimoxazole
5 mg of TMZ/kg/day PO bid 3 day/wk (Fri-Sat-Sun)
Record date given

Week
Note
Week
wk 9 (____/____/____)
wk 25 (____/____/____)
wk 11 (____/____/____)
wk 27 (____/____/____)
wk 13 (____/____/____)
wk 29 (____/____/____)
wk 15 (____/____/____)
wk 31 (____/____/____)
wk 17 (____/____/____)
wk 33 (____/____/____)
wk 19 (____/____/____)
wk 35 (____/____/____)
wk 21 (____/____/____)
wk 37 (____/____/____)
wk 23 (____/____/____)
wk 39 (____/____/____)
Note
F/U CBC, LFT q 2wk

F/U BUN/Cr, Serum ferritin monthly
Keep Cyclosporine level 150-200 ng/ml
End of therapy _______/________/________
310

311

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(The Thai Pediatric Oncology Group: ThaiPOG)

(The Thai Society of Hematology)

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

(Thai Pediatric Oncology group) 15

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Acute Lymphoblastic Leukemia (ALL)

High Risk (HR)

Acute Lymphoblastic Leukemia (ALL): Management guideline

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Standard Risk (SR)

Very High Risk (VHR)

High Risk (HR)

Induction failure and

Acute Lymphoblastic Leukemia (ALL): Treatment Schema

Thai Pediatric Oncology Group

Treatment schema: Infant ALL

Schema for treatment of relapsed ALL (ThaiPOG-ALL-13-REL)

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Acute Lymphoblastic Leukemia (ALL): Methotrexate infusion guideline

Thai Pediatric Oncology Group

Acute Lymphoblastic Leukemia (ALL): Methotrexate infusion guideline

Thai Pediatric Oncology Group

Any MTX level

Any MTX level

Any MTX level

Any MTX level

Acute Lymphoblastic Leukemia (ALL): Methotrexate infusion guideline

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Acute Lymphoblastic Leukemia (ALL): Supportive care guideline

Thai Pediatric Oncology Group

Anthracycline dose (mg/m2)

Acute Lymphoblastic Leukemia (ALL): Supportive care guideline

ECHO(MUGA)/EKG interval (years)

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group

Thai Pediatric Oncology Group