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Ped CA Protocol 2014 PDF
Ped CA Protocol 2014 PDF
2557
(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
1 .. 2557
1,000
. 02-943-8787, 02-508-1114
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ISBN 978-616-91631-1-4
Thai Pediatric Oncology Group
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Thai Pediatric Oncology Group
Thai Pediatric Oncology Group
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disease management
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solid tumor
solid tumor
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Thai Pediatric Oncology Group
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disease management . 2555
histiocytosis
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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
Treatment protocol for very high risk acute lymphoblastic leukemia [Thai-POG ALL 1303] .......... 29 30
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
Thai Pediatric Oncology Group
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 ThaiPOG-
NHL13-BL protocol .................................................................................................................... 143
Appendix II: Supportive care guidelines for high dose methotrexate administration for ThaiPOG-
NHL13-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-BL-
SR] ............................................................................................................................................ 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- NHL-
13-ALCL-SR] ............................................................................................................................. 168
Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL-13-
ALCL-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
Thai Pediatric Oncology Group
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 retinoblastoma [ThaiPOG-RB-13-02] ...................................................... 220
Treatment protocol for retinoblastoma [ThaiPOG-RB-13-03] ...................................................... 222
Treatment protocol for retinoblastoma [ThaiPOG-RB-13-04] ...................................................... 224
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
Treatment protocol for Wilms tumor [ThaiPOG-WT-13-02] ........................................................ 232
Treatment protocol for Wilms tumor [ThaiPOG-WT-13-03] ........................................................ 236
Treatment protocol for Wilms tumor [ThaiPOG-WT-13-04] ........................................................ 240
(Recommended imaging studies for follow-up) ........................................... 244
Hepatoblastoma .............................................................................................................................245
Data entry form for hepatoblastoma ........................................................................................... 245
PRETEXT (Pre-treatment extent of disease) staging system ..................................................... 246
Thai Pediatric Oncology Group
High dose cisplatinum (CDDP) administration protocol .............................................................. 247
Post-treatment evaluation .......................................................................................................... 248
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
Post-treatment evaluation .......................................................................................................... 281
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
Thai Pediatric Oncology Group
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
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 2
Thai Pediatric Oncology Group
Treatment Schema
Protocol assignment and treatment schema for new ALL patient
Acute Lymphoblastic Leukemia (ALL)
Standard Risk (SR) High Risk (HR) Very High Risk (VHR) Infant ALL
See Infant
Induction (3 drugs) Ph + ALL Induction (4 drugs)
protocol
Follow Ph+ ALL protocol
DI Augmented DI
VHR
IM-II
Maintenance HR
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.
PH-Induction INF-Re-Induction
PH-Consolidation-I
PH-Consolidation-II
INF-Consolidation
PH-IM-I
Donor - Donor +
LR-INF-Continuation-I HR-INF-Continuation-I
PH-DI-I HSCT HR-INF-Continuation-II
PH-DI-I HR-INF-Continuation-III
LR-INF-Continuation-II HR-INF-Continuation-IV
HR-INF-Continuation-V
PH-IM-II
INF-Maintenance INF-Maintenance
PH-Maintenance
Schema for treatment of relapsed ALL (ThaiPOG-ALL-13-REL)
Standard Intermediate High
MRD POS
NEG
Phase 2 Phase 2
Phase 3
Phase 3
Localized
radiotherapy MRD
POS
NEG
Phase 5
Phase 4 Allo SCT
Phase 6
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity 4
Thai Pediatric Oncology Group
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
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity 5
Thai Pediatric Oncology Group
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
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity 6
Thai Pediatric Oncology Group
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.
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity 7
Thai Pediatric Oncology Group
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.
Acute Lymphoblastic Leukemia (ALL): Dose modification guidelines for chemotherapy toxicity 8
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Guidelines for Tyrosine Kinase Inhibitors administration 13
Thai Pediatric Oncology Group
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): Treatment protocol for standard risk acute lymphoblastic leukemia 16
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia 17
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia 18
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia 19
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia 20
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for standard risk acute lymphoblastic leukemia 21
[Thai-POG ALL 1301]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 23
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 24
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 25
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 26
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 27
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for high risk acute lymphoblastic leukemia [Thai- 28
POG ALL 1302]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 29
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Treatment protocol for very high risk acute lymphoblastic leukemia [Thai-POG ALL 1303]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 30
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 31
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 32
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 33
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 34
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 35
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 36
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 37
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for very high risk acute lymphoblastic leukemia 38
[Thai-POG ALL 1303]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 39
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Treatment protocol for Philadephia chromosome positive acute lymphoblastic leukemia [Thai-
POG ALL 1304]
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 40
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 41
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 42
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 43
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 44
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 45
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 46
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 47
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 48
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 49
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 50
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 51
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for Philadephia chromosome positive acute 52
lymphoblastic leukemia [Thai-POG ALL 1304]
Thai Pediatric Oncology Group
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 :
Inclusion criteria
day 1 8 15 22 29
Date given
Dexamethasone .................................... tab PO TID
Mitoxantrone ................................................... mg IV
Vincristine ....................................................... mg IV
L-asp............ U IM
MTX................................................................ mg IT* T# T#
#Intrathecal chemotherapy for CNS 3 disease, to be given weekly until CSF ve for 2 consecutive times (at least 4 doses)
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 54
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
day 1 8 15 22
Date given
Dexamethasone . tab PO BID
Vincristine ... mg IV push
Methotrexate . mg IV drip 24 hr
L-asp . UIM
Cyclophosphamide .. mg IV xxxxx
Etoposide .. mg IV +++++
MTX .. mg* T
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 55
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
day 1 8 15 22
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
MTX .. mg* T T
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 56
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
Date given
Fludarabine . mg IV drip daily
Cytarabine . mg IV Q 12 hr
Idarubicin .. mg IV
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 57
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
day 1 8 15 22 29 36 43 50
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 + +
MTX .. mg* T T
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 58
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
day 57 64 71 78 85 92 99 106
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 + +
MTX .. mg* T T
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 59
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW................................kg Ht..............................cm BSA..............................m2
Date given
Dexamethasone ... tab PO BID
Vincristine ..... mg IV push
6-mercaptopurine tab PO hs
Methotrexate tab PO hs
MTX .. mg* T
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for relapsed acute lymphoblastic leukemia 60
[Thai-POG ALL 1305]
Thai Pediatric Oncology Group
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 Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 62
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 63
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 64
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 65
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 66
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 67
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infant acute lymphoblastic leukemia 68
[Thai-POG ALL 1306]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for low risk infanthigh
intermediate/ acuterisk infant acute 69
lymphoblastic leukemia [Thai-POG ALL 1306]
1307]
Thai Pediatric Oncology Group
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
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 71
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 72
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 73
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 74
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 75
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 76
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 77
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 78
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 79
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Lymphoblastic Leukemia (ALL): Treatment protocol for intermediate/ high risk infant acute 80
lymphoblastic leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
Acute Myeloid Leukemia (AML): Treatment protocol for intermediate/ high risk infant acute lymphoblastic 81
leukemia [Thai-POG ALL 1307]
Thai Pediatric Oncology Group
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
Treatment schema
Protocol assignment for new AML patient:
No Yes
No Yes
LR-Induction-II HR-Induction-II
LR-Consolidation-I HR-Consolidation-I
-Donor + Donor
Consolidation#1
Consolidation#2
+/- Salavage RX
Maintenance
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
Acute Myeloid Leukemia (AML): Dose modification guidelines for chemotherapy toxicity 84
Thai Pediatric Oncology Group
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.
Acute Myeloid Leukemia (AML): Dose modification guidelines for chemotherapy toxicity 85
Thai Pediatric Oncology Group
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.
Acute Myeloid Leukemia (AML): Dose modification guidelines for chemotherapy toxicity 86
Thai Pediatric Oncology Group
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.
Hospital HN BW kg Ht cm BSA m2
Disease Status: Treatment schema:
Initial WBC:
Induction-I
FAB Morpholgy (M0-M7):
Immuno-phenotype: End of Induction eval
CNS status (circle one): Positive Negative
Isolated Myeloid sarcoma (circle one): Yes No High Risk features
If yes, describe:
Cytogenetics: FISH: No Yes
Mutation Status: FLT3 NPM1 CEBP-A
LR-Induction-II HR protocol
End of Induction evaluation:
BMA (circle): M1 M2 M3
LR-Consolidation-I
MRD (circle): Negative Positive
Imaging:
LR-Consolidation-II
Post induction risk assignment (check one):
Low Risk
Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 90
1301]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Week 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C mg Q 12 H IV CCCCCCC C Start next
course
IDA mg IV I I I
(Consolidation-I)
IT-ARA-C mg T (T) (T) (T) (T) (T)
on day 29 or
Investigation: when blood
CBC/diff + + + + count
CSF cell count/ cytospin + (+) + (+) + (+) parameters are
BUN, Cr, TB,DB, AST, ALT + + + + met
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 91
1301]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: LR- CONSOLIDATION -I (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
Start next
ARA-C mg Q 12 H IV CCCCC course
ETOP mg IV E EE EE (Consolidation-
IT-ARA-C mg T II) on day 29 or
when blood
Investigation: count
CBC/diff + + + + parameters are
CSF cell count/ cytospin +
BUN, Cr, TB,DB, AST, ALT + + + + met
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Drug Route Dosage Days
Cytarabine IV over 1-3 hours 1,000 mg/m2/dose Q 12 hours or Days 1-5
(HD ARAC) 33 mg/kg/dose Q 12 hours if BSA < 0.6 m2
Etoposide (ETOP) IV over 60 -120 minutes 150 mg/m2/dose once a day or Days 1-5
5 mg/kg/dose once a day if BSA < 0.6 m2
Intrathecal Cytarabine IT Age(yrs ) Dose Day 1
(IT ARA-C) 0-0.99 20 mg
1-1.99 30 mg
2-2.99 50 mg
3 70 mg
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
Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 92
1301]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase IV: LR- CONSOLIDATION - II (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCCC
IT-ARA-C _______ mg T
End of
Investigation: therapy
CBC/diff + + + + evaluation.
CSF cell count/ cytospin +
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Acute Myeloid Leukemia (AML): Treatment protocol for low risk acute myeloid leukemia [Thai-POG AML 93
1301]
Thai Pediatric Oncology Group
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
Patient eligibility:
Acute Myeloid Leukemia with
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 Age Sex
Hospital HN BW kg Ht cm BSA m2
Disease Status:
Initial WBC: Morphology: FAB (M0-M7):
CNS status (circle one): Positive Negative Immuno-phenotype:
Isolated Myeloid sarcoma (circle one): Yes No Treatment schema:
If yes, describe:
Induction-I
Cytogenetics: FISH
HR features
Mutation Status: FLT3 NPM1 CEBP-A HR-Induction-II
End of Induction evaluation:
BMA (circle): M1 M2 M3 HR-Consolidation-I
MRD (circle): Negative Positive + Donor
-Donor
Imaging:
HR-Consolidation-II HSCT
Post induction Management (check one):
HSCT donor available: HSCT after HR-Consolidation I
Donor type: (circle one) MRD MUD MUCB MMRD Haplo
HSCT donor not available: HR protocol chemotherapy
End of therapy date: / /
Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 94
1302]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I: INDUCTION - I (5 weeks) Date start:
Week 1 2 3 4 5
Day 1 8 15 22 28 29
Date due
Date given
Medication: Start next
ARA-C _______ mg Q 12 H IV CCCCCCC CCC course
IDA _______ mg IV I I I (Induction-II)
IT-ARA-C _______ mg T (T) (T) (T) (T) (T) on day 29 or
when blood
Investigation: count
CBC/diff + + + + + parameters
CSF cell count/ cytospin + (+) + (+) + (+)
BUN, Cr, TB,DB, AST, ALT + + + + + are met
BM Aspiration +
Biopsy and MRD (optional) +
ECHOor MUGA and EKG (optional) +
Drug Route Dosage Days
Cytarabine IV over 30 minutes 100 mg/m2/dose Q 12 hours or Days 1-10
(ARA-C IV) 3.3 mg/kg/dose Q 12 hours if BSA < 0.6 m2
IDArubicin (IDA) IV drip in 4 hours 12 mg/m2/dose once a day or Days 1,3,5
0.4 mg/kg/dose once a day if BSA < 0.6 m2
Intrathecal Cytarabine IT Age(yrs ) Dose Day 1
(IT ARA-C) 0-0.99 20 mg
1-1.99 30 mg
2-2.99 50 mg
3 70 mg
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 Normal cytogenetic with MRD >= 0.1% at the end
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]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase II: HR-INDUCTION - II (4 weeks) 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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCCC
MITOX _______ mg IV MMMM Start next course
IT-ARA-C _______ mg T (T) (T) (T) (T) (T) (Consolidation-I)
on day 29 or
Investigation: when blood
CBC/diff count parameters
CSF cell count/ cytospin are met
BUN, Cr, TB,DB, AST, ALT
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG optional)
Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 96
1302]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: HR- CONSOLIDATION - I (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCCCC Start next
course
ETOP _______ mg IV E EE EE (Consolidation-
IT-ARA-C _______ mg T II or HSCT) on
day 29 or when
Investigation: blood count
CBC/diff + + + + parameters are
CSF cell count/ cytospin + met
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional) +
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 97
1302]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase IV: HR- CONSOLIDATION - II (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CC CC
L-ASP _______ IU IM A A
Investigation:
End of therapy
CBC/diff
evaluation.
CSF cell count/ cytospin
BUN, Cr, TB,DB, AST, ALT
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional)
CrCl if Cr> 2 mg/dl or 2 xULN
Acute Myeloid Leukemia (AML): Treatment protocol for high risk acute myeloid leukemia [Thai-POG AML 98
1302]
Thai Pediatric Oncology Group
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 Total Pages: 8
Open date: January 2014
Patient eligibility:
De novo Acute Myeloid Leukemia
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Disease Status:
Cytogenetics: FISH
+/-Induction-II
End of Induction evaluation:
Imaging:
Consolidation-II
Post Induction Management (check one): - Donor + Donor
Describe:
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 99
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I: INDUCTION (5 weeks) Date start:
Week 1 2 3 4 5
Day 1 8 15 22 28 29
Date due
Date given
Medication: Start next
ARA-C _____ mg Q 24 H IV CCCCCCC course on
IDA _______ mg IV III day 29 or
TIT _______ mg T when
blood
Investigation:
count
CBC/diff + + + + +
CSF cell count/ cytospin + parameters
BUN, Cr, TB,DB, AST, ALT + + + + + are met
BM Aspiration +
Biopsy and MRD (optional) +
ECHOor MUGA and EKG (optional) +
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 100
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I/II: INDUCTION-II (4 weeks) Date start:
Begin on Day 29 of Induction-I regardless of blood count
Week 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 24 H IV CCCCCCC
IDA _______ mg IV III Start next course
TIT _______ mg T (Consolidation-I)
on day 29 or
Investigation: when blood
CBC/diff + + + + count parameters
CSF cell count/ cytospin + are met
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration +
Biopsy and MRD (optional) +
ECHOor MUGA and EKG (optional +
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 101
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase II: CONSOLIDATION-I (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCC
Start next course
ETOP mg IV EEEE (Consolidation-II)
TIT mg T on day 29 or
Investigation: when blood count
CBC/diff + + + + parameters are
CSF cell count/ cytospin + met
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Drug Route Dosage Days
Cytarabine (HD ARAC) IV over 1-3 hours 3,000 mg/m2/dose Q 12 hours or Days 1-3
100 mg/kg/dose Q 12 hours if BSA < 0.6 m2
Etoposide (ETOP) IV over 60 -120 minutes 125 mg/m2/dose once a day or Days 2-5
5 mg/kg/dose once a day if BSA < 0.6 m2
Intrathecal Therapy IT Age(yrs) MTX Ara-C HC Day 1
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
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.
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 102
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: CONSOLIDATION-II (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
Start next
ARA-C _______ mg Q 12 H IV CC CC course
L-ASP _______ IU IM A A (Consolidation-
TIT_______ mg T III or HSCT) on
day 29 or when
Investigation: blood count
CBC/diff + + + + parameters are
CSF cell count/ cytospin + met
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Drug Route Dosage Days
Cytarabine IV over 3 hours 3,000 mg/m2/dose Q 12 hours or Days 1,2 and 8,9
(HD ARAC) 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2
L-Asparaginase IM 6,000 IU/m2/dose once a day or Days 2 and 9. To
(L-ASP) 200 IU/kg/dose once a day if BSA < 0.6 m2 be given 6 hours
after the start of
4th and 8th dose
of ARA-C
Intrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1
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
Note
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.
End of consolidation-II treatment assignment:
o Available match related donor HSCT
o No available match related donor continue consolidation-III
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 103
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase IV: CONSOLIDATION-III (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CCC
ETOP _______ mg IV EEEE
TIT _______ mg T Start next course
(Consolidation-IV)
Investigation: on day 29 or when
CBC/diff + + + + blood count
CSF cell count/ cytospin + parameters are met
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 104
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase V: CONSOLIDATION-IV (4 weeks) Date start:
Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/l and
Platelets>75,000 cells/ l.
Week 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication:
ARA-C _______ mg Q 12 H IV CC CC
L-ASP _______ IU IM A A End of therapy
evaluation or
TIT _______ mg T
CNS treatment
Investigation: program for CNS
CBC/diff + + + + disease patient
CSF cell count/ cytospin +
BUN, Cr, TB,DB, AST, ALT + + + +
BM Aspiration
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Drug Route Dosage Days
Cytarabine IV over 3 hours 3,000 mg/m2/dose Q 12 hours or Days 1,2 and 8,9
(HD ARAC) 100 mg/kg/dose Q 12 hours if BSA < 0.6 m2
L-Asparaginase IM 6,000IU/m2/dose once a day or Days 2 and 9. To
(L-ASP) 200 IU/kg/dose once a day if BSA < 0.6 m2 be given 6 hours
after the start of
4th and 8th dose
of ARA-C
Intrathecal Therapy IT Age(yrs ) MTX Ara-C HC Day 1
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
Note
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.
End of therapy evaluation: CBC, MUGA/ECHO, BMA/clot section or biopsy, UA, Elyte, CA, Phos,
BUN, Cr, AST/ALT, TB/DB.
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 105
02-08]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase VI: CNS- Treatment program (for CNS disease patient only) Date start:
Begin on Day 29 of Consolidation-III. It is suggested but not required to have ANC > 1,000 cells/l and
Platelets>75,000 cells/ l.
Radiation field :( )
Number of fractions :( )
Date start :( )
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.
Acute Myeloid Leukemia (AML): Optional treatment protocol for acute myeloid leukemia [Thai-POG AML- 106
02-08]
Thai Pediatric Oncology Group
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
Patient eligibility:
Acute Myeloid Leukemia with
o PML/RARa fusion gene from PCR, FISH or cytogenetic
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Disease Status: Treatment schema:
Initial WBC: FAB Morpholgy (M0-M7): Induction
Immuno-phenotype:
CNS status (circle one): Positive Negative N Day#45 evaluation
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 107
0106]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I: INDUCTION- (6-13 weeks) Date start:
Week 1 2 3 4 5 6 7 8 9 10 11 12
Day 1 15 36 45 57 78 90
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 108
0106]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase II: Consolidation- (8 weeks) Date start:
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 1 2 3 3 4 5
Day 1 8 15 16 22 29
Date due Cycle 1 /Cycle 2
Date given / Start consolidation
cycle 2 on day 29
Medication: of consolidation
ATRA _______ mg Q 12 H PO cycle 1.
IDA _______ mg IV I I I Start Next course
(Salvage therapy
Investigation: or maintenance)
CBC/diff + + + + on day 29 of
BUN, Cr, TB,DB, AST, ALT + + consolidation cycle
BM Aspiration
2
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
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
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 109
0106]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: Salvage Therapy- (4 weeks) Date start:
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 1 2 3 4 5
Day 1 8 15 22 29
Date due
Date given
Medication: Start next
ARA-C _______ mg Q 12 H IV CCC course
Investigation: Maintenance on
CBC/diff + + + + day 29 or when
BUN, Cr, TB,DB, AST, ALT + + + + blood count
BM Aspiration parameters are
met
Biopsy and MRD (optional)
ECHOor MUGA and EKG (optional) +
CrCl if Cr> 2 mg/dl or 2 xULN +
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 110
0106]
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase IV: Maintenance- (12 weeks) Date start:
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 1 2 3 3 4 5 6 7 8 9 10 11 12 13
Day 1 8 15 16 22 29 36 43 50 57 64 71 78 85
Medication:
ATRA______ mg po BID
6-MP _____ mg PO daily Repeat
next cycle
MTX _______ mg PO M M M M M M M M M M M M for total of
Investigation: 8 cycles
CBC/diff + + +
BUN, Cr, TB,DB, AST, ALT +
Drug Route Dosage Days
All-Trans-Retinoic-Acid (ATRA) PO 25 mg/m2/day BID Days 1-15
6-Mercaptopurine (6-MP) PO 50 mg/m2/dose Day 1-84
2
Methotreaxate (MTX) PO 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 BSA Medication dosage Note:
given
Weight ______ kg ATRA ________ mg po BID
1 Height ______ cm 6-MP _________ mg po daily
BSA _______ m2 MTX ________ mg po weekly
Acute Myeloid Leukemia (AML): Treatment protocol for acute promyelocytic leukemia [Thai-POG APL 111
0106]
Thai Pediatric Oncology Group
Lymphoma
Hodgkin disease
Risk stratification
Low risk (LR) Intermediate Risk (IR) High Risk (HR)
Stage I-A with no bulk Stage I-E, I-B and I-A with bulk Stage III-B
Stage II-A with no bulk Stage II-E, II-B and II-A with bulk Stage IV-B
Stage III-A
Stage IV-A
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
Treatment schema
Hodgkin Disease
CT/PET/Gal CT/PET/Gal
CR IFRT
ABVE-PC x 2 cycle
Follow up CR PR/SD/PD
CT/PET/Gal
PD SD/PR/CR
PD
Salvage protocol PR IFRT
Follow up CR
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
MTX induced (up to 3 High dose MTX can cause hyperbillirubinemia and
weeks after MTX) transaminitis that last up to 2 weeks that will not be
consider toxicity required discontinuation of the
drug
Ifosphamide/Etoposide
Toxicity Grade Action
Myelosuppression On day 1 of cycle: ANC < 750 Delayed until recovery
or Plt < 75,000
Mucositis Grade 4 (severe ulceration, Reduce ETOP by 50%
require TPN or intubation) after
previous cycle or repeated
Grade 3 (painful erythema,
edema or ulcer requiring IV)
Renal toxicity- Serum Cr > 1.5 x baseline or Delay for 1 week. If renal function does not
Glomerular GFR < 70 ml/min/1.73 m2 improve, discontinue IFOS, confirm GFR and
consider substituting Cyclophosphamide and
MESNA at 500 mg/m2 x 5 days
Grade 3 (confusion or delirium Stop IFOS for this cycle. Decrease IFOS by
or obtundation or stupor; 20% during next cycle. If persists, reduce by
difficult to arouse, interfering a further 20%.
with daily living)
Grade 4 (harmful to others or Stop IFOS for this cycle and no further IFOS.
self, require hospitalization or Give methylene blue at 2 mg/kg (Max: 50
coma) 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.
Neurological Grade 2 (self-limited and Stop IFOS for this cycle. Continue future
Toxicity- Seizure consciousness is preserved) cycle at the same dose.
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.
Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301]
Protocol name: Thai-POG HOD 1301 Reference: COG AHOD 0431
Protocol for: Low Risk Hodgkin Disease Total Pages: 6
Patient eligibility:
Low Risk Hodgkins Disease:
CR PR SD PD
CT/PET/Gal
IFRT: (circle one) Yes No CR
PR, SD
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 125
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I: LR-INDUCTION-I (3 weeks) Date Start:___________
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 22
Date due
Date given
Medication:
DOX _______ mg IV D D Start
BLEO _______/______ mg IV B B* Induction-II
on day 22
VCR _______ mg IV V V
or when
ETOP _______ mg IV E E E blood count
Investigation: parameters
CBC/diff + + + are met.
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
ECHO or MUGA and EKG +
PFT +
Note
CR = complete remission, PR= partial remission, SD = stable disease, PD = progressive disease
RER = Rapid Early Response, SER = Slow Early Response
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 protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 126
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase II: LR-INDUCTION-II (3 weeks) Date Start:___________
Start Induction-II on Day 22 of Induction-I and ANC 750/ul and PLT 75,000/ul whichever occurs later.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 21 22
Date due
Date given
Medication: Start Next
DOX _______ mg IV D D course
BLEO _______/______ mg IV B B* Consolidation-I
on day 22 or
VCR _______ mg IV V V when blood
ETOP _______ mg IV E E count
Investigation: parameters are
CBC/diff + + + met.
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB
+ + +
CT C/A/P or PET CT
+
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 127
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: LR- CONSOLIDATION -I (3 weeks) Date Start:___________
Start Consolidation-I on Day 22 of Induction-II and ANC 750/ul and PLT 75,000/ul whichever occurs
later.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 22
Date due
Date given
Medication:
DOX _______ mg IV D D Start
Consolidation-
BLEO _______/______ mg IV B B* II on day 22 or
VCR _______ mg IV V V when blood
ETOP _______ mg IV E E count
Investigation: parameters are
met.
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
Echo or MUGA and EKG +
PFT +
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 128
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase IV: LR- CONSOLIDATION -II (3 weeks) Date Start:___________
Start Consolidation-II on Day 22 of Consolidation-I and ANC 750/l and PLT 75,000/l whichever
occurs later.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 21 22
Date due
Date given
Medication: Proceed to
next phase of
DOX _______ mg IV D D
therapy (IFRT
BLEO _______/______ mg IV B B* or End of
VCR _______ mg IV V V therapy)
ETOP _______ mg IV E E E according to
End of
Investigation:
Induction
CBC/diff + + + disease
ESR, ELyte, BUN, Cr, AST, ALT, + + + status
TB,DB +
CT C/A/P or PET CT
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 129
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase V: INVOLVED FIELD RADIATION THERAPY (IFRT): For SER patient only
Date Start:____
Radiation field :( )
Total radiation dose :( )
Number of fractions :( )
Date start :( )
Last day of radiation :( )
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
Lymphoma: Treatment protocol for low risk Hodgkin disease [Thai-POG HOD 1301] 130
Thai Pediatric Oncology Group
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
Patient eligibility:
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):
Site involvement: RER SER
Pathologic subtype: HR-Consolidation-I HR-Intensification-I
Disease stage: Risk group:
Post Induction Evaluation: CR PR SD PD HR-Consolidation-II HR-Intensification-II
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:
CR PR SD PD HR-Consolidation-II
CR
IFRT Date:
Total dose CT/PET/Gal
Post IFRT evaluation: (circle one)CR PR SD PD CR, PR, SD
End of therapy date: CR, PR, SD IFRT 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
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase I: HR-INDUCTION-I (3 weeks) Date Start:___________
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 22
Date due
Date given
Medication:
DOX _______ mg IV D D
BLEO _______/______ mg IV B B* Start
VCR _______ mg IV Induction-
V V II on day
ETOP _______ mg IV E E E 22 or when
PRED _____ mg PO BID blood
CPM _______ mg IV C C count
G-CSF _______ mcg SQ/IV parameters
G G are met.
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
ECHO or MUGA and EKG +
PFT
+
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 132
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Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase II: HR-INDUCTION-II (3 weeks) Date Start:___________
Last day of G-CSF:
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.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 21 22
Date due
Date given
Medication:
DOX _______ mg IV D D
BLEO _______/______ mg IV B B* Start Next
VCR _______ mg IV course
V V (Intensification-
ETOP _______ mg IV E E I or
Consolidation-I)
PRED _____ mg PO BID on day 22 or
when blood
CPM _______ mg IV C C count
parameters are
G-CSF _______ mcg SQ/IV G G met.
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
CT C/A/P or PET CT +
BM aspiration and biopsy (+)
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 133
Thai Pediatric Oncology Group
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 Date Start:___________
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.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 22
Date due
Date given
Medication:
DOX _______ mg IV D D
BLEO _______/______ mg IV B B* Start
VCR _______ mg IV V V Consolidation-
ETOP _______ mg IV E E E II on day 22 or
PRED _____ mg PO BID when blood
count
CPM _______ mg IV C C parameters are
G-CSF _______ mcg SQ/IV G G met.
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB
Echo or MUGA and EKG
+ + +
PFT +
+
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Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase VI: HR-Consolidation-II (3 weeks) Date Start: 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.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 21 22
Date due
Date given
Medication:
DOX _______ mg IV D D
BLEO ______/______ mg IV Proceed to
B B* next phase of
VCR _______ mg IV V V therapy
ETOP _______ mg IV (IFRT or
E E E salvage
PRED _____ mg PO BID protocol)
according to
CPM _______ mg IV C C End of
G-CSF _______ mcg SQ/IV G G Consolidation
evaluation
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
CT C/A/P or PET CT +
BM aspiration and biopsy (+)
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 135
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase III: HR-INTENSIFICATION-I (3 weeks):
Only for SER: start after Induction-II 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.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 9 10 15 22
Date due
Date given
Medication:
HD-MTX _______ mg IV M
LCV _______ mg IV/PO LLLLLLLLLL
LL Start
ETOP _______ mg IV E E E Intensification-II
IFOS _______ mg IV I I I on day 22 or
MESNA _______ mg IV SSS SSS SSS when blood
count
DEX _______ mg IV DDD DDD
DDD parameters are
G-CSF _______ mcg SQ/IV G met.
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
Echo or MUGA and EKG +
PFT +
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 136
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht 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.
Week 1 2 3 4
Day 1 2 3 4 5 6 7 8 15 21 22
Date due
Date given
Medication:
HD-MTX _______ mg IV M
LCV _______ mg IV/PO LLLLLLLLLLL
L Start next phase
ETOP _______ mg IV E E E (Consolidation-I
IFOS _______ mg IV I I I or Salvage) on
day 22 or when
MESNA _______ mg IV SSS SSS SSS
blood count
DEX _______ mg IV DDD DDD DDD parameters are
G-CSF _______ mcg SQ/IV G met.
Investigation:
CBC/diff + + +
ESR, ELyte, BUN, Cr, AST, ALT, TB,DB + + +
CT C/A/P or PET CT +
BM aspiration and biopsy (+)
Drug Route Dosage Days
High-dose Methotrexate IV drip in 4 hours 8,000 mg/m2/day Day 1
(HD-MTX)
Leucovorin (LCV) IV/PO 15 mg/m2/dose q 6 hours Day 2, 3, 4
Etoposide (ETOP) IV over 60-120 minutes 200 mg/m2/day Day 2, 3, 4
Ifosfamide (IFOS) IV over 4 hours 2,000 mg/m2/day Day 2, 3, 4
Mesna IV 500 mg/m2/dose Day 2, 3, 4
At hour 0, 3, 6 of IFOS
Dexamethasone (DEX) IV 40mg/m2day divided in 3 Day 1, 2, 3
dose q 8 hours
G-CSF SubQ or IV 5 mcg/kg/day
Day 4 then daily
Note:
Begin G-CSF 24 hours after completion of last dose of Etoposide and continue until ANC > 1,000/ul
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
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 137
Thai Pediatric Oncology Group
Patients name Age Sex
Hospital HN BW kg Ht cm BSA m2
Phase V: INVOLVED FIELD RADIATION THERAPY (IFRT):
For all IR and HR Hodgkin lymphoma patients
Radiation field :( )
Total radiation dose :( )
Number of fractions :( )
Date start :( )
Last day of radiation :( ) 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
Lymphoma: Treatment protocol for intermediate/ high risk Hodgkin disease [Thai-POG HOD 1302] 138
Thai Pediatric Oncology Group
Lymphoma: Treatment plan for patiants with mature B-cell lymphoma 141
Thai Pediatric Oncology Group
Treatment plan
Risk group Pre-Phase Intensive phase
Low risk COP A1 B1 A2
Standard risk COP A1 B1 A2 B2 A2 B3
High risk COP AM1 BM1 AM2 BM2 AM2 BM3
Intrathecal Treatment
Age Methotrexate Hydrocortisone Ara-C
<1 6 mg 4 mg 16 mg
1-2 8 mg 6 mg 20 mg
2-3 10 mg 8 mg 24 mg
>3 12 mg 10 mg 30 mg
Lymphoma: Treatment plan for patients with anaplastic large cell lymphoma 142
Thai Pediatric Oncology Group
Lymphoma: Appendix I: Supportive care guidelines for high dose methotrexate administration for 143
ThaiPOG-NHL13-BL protocol
Thai Pediatric Oncology Group
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
3) 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.
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
24 hrs < 30 mol/L -
42 hrs 15 mg/m2 IV
48 hrs < 0.25 mol/L 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.
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ThaiPOG-NHL13-ALCL protocol
Thai Pediatric Oncology Group
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.
3) 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.
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.
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ThaiPOG-NHL13-ALCL protocol
Thai Pediatric Oncology Group
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.
Lymphoma: Appendix II: Supportive care guidelines for high dose methotrexate administration for 146
ThaiPOG-NHL13-ALCL protocol
Thai Pediatric Oncology Group
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
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Inclusion Criterla Completlely stage I Completely resected abdominal stage II lesion
Days 1 2 3 4 5 6 7
Prednisolone
Vincristine
Cyclophosphamide
Doxorubicin
G-CSF
Given dose/day Drug Dosage
.mg Vincristine 2 mg/m2 (max single dose 2 mg) IV bolus on Day 1 and 6
.mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7
inclusive.
.mg 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
.mg Doxorubicin 60 mg/m2 as a 6 hour infusion, after the first dose of
cyclophosphamide on Day 1
..mcg 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.
Low Risk Group Date Remarks
COPAD Course 1
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]
Thai Pediatric Oncology Group
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 150
BL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 1 2 3 4 5 6 7
Vincristine
Prednisolone
Methotrexate
Leucovorin
Cyclophosphamide
Doxorubicin
IT MTX
IT HC
G-CSF
Rituximab
Given dose/day Drug Dosage
.mg Vincristine 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1
.mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7 inclusive
.mg Methotrexate 3,000 mg/m2 in dextrose 5% as IV infusion over 3 hours on Day 1.
...mg/dose Leucovorin 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 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 60-
100% of the daily cyclophosphamide dose
.mg Doxorubicin 60 mg/m2 as a 6 hour infusion, after the first dose of
cyclophosphamide.
.mg 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
..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.
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 151
BL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 2
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 152
BL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Days 1 2 3 4 5 6 7
Methotrexate
Leucovorin
Cytarabine
IT MTX
IT-Ara-C
IT HC
G-CSF
Rituximab
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 153
BL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
CYM Course 2
Lymphoma: Treatment protocol for standard risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13- 154
BL-SR]
Thai Pediatric Oncology Group
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 3 4 5 6 7
Cyclophosphamide
Vincristine
Prednisolone
IT MTX
IT HC
IT Ara-C
Leucovorin
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 155
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 156
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
High Risk Group - Induction Date Remarks
COPADM8 Course 1
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 157
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 2 mg/m2 (max dose 2 mg) as IV bolus on Day 1
.mg Prednisolone 60 mg/m2/day (divided into bid doses) orally on Days 1-7
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)
...mg/dose Leucovorin 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 60 mg/m2 as a 6 hour infusion, after the first dose of
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.
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 158
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 159
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 160
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 161
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 162
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 163
HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for high risk mature B-cell non-Hodgkin lymphoma [ThaiPOG-NHL-13-BL- 164
HR]
Thai Pediatric Oncology Group
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Inclusion criteria
Stage I disease completely resected
Low Risk Group Treatment Plan (P A1 B1 A2 )
Lymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 165
LR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 1 2 3 4 5
Dexamethasone
Methotrexate
IT-MHC
Ifosfamide
Mesna
Cytarabine
Etoposide
Lymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 166
LR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Course B1
Course A2
Lymphoma: Treatment protocol for low risk anaplastic non-Hodgkin lymphoma [ThaiPOG- NHL-13-ALCL- 167
LR]
Thai Pediatric Oncology Group
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Lymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 168
NHL-13-ALCL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Standard Risk : Intensive phase (A1 B1 A2 B2 A3 B3)
Lymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 169
NHL-13-ALCL-SR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Lymphoma: Treatment protocol for standard risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- 170
NHL-13-ALCL-SR]
Thai Pediatric Oncology Group
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
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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)
Lymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 171
13-ALCL-HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
High Risk: Intensive phase (AM1 BM1 AM2BM2 AM3 BM3)
Days 1 2 3 4 5
Dexamethasone
Methotrexate
Ifosfamide
Mesna
Cytarabine
Etoposide
Lymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 172
13-ALCL-HR]
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Lymphoma: Treatment protocol for high risk anaplastic large cell non-Hodgkin lymphoma [ThaiPOG- NHL- 173
13-ALCL-HR]
Thai Pediatric Oncology Group
CNS Germ Cell Tumor
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) .....................................2
Age ............. yr...............m. BW...........kg Ht...............cm. BSA...................m
() .................................
History
Physical examination
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
Thai Pediatric Oncology Group
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
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
Cycle Agent (s) Dose (s) 2
1,2,3 Ifosfamide 1,800 mg/m IV drip in 1-2 hour daily Day 1-3
Mesna 400 mg/m2 prior to ifosfamide infusion and then at 3,6,9,12 hr
after ifosfamide infusion
Carboplatin 560 mg/m2 IV drip in 1 hour Day 1
Etoposide 150 mg/m22 IV drip in 2 hour daily Day 1-3
4,5,6,7,8 Carboplatin 560 mg/m2 IV drip in 1 hour Day 1
Etoposide 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 Date BSA Ifosafmide Carboplatin Etoposide
1
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
Thai Pediatric Oncology Group
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
CNS Germ Cell Tumor: Treatment protocol for CNS non-germinoma [ThaiPOG-BT-13-NGCT] 177
Thai Pediatric Oncology Group
Medulloblastoma
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) .....................................2
Age ............. yr...............m. BW...........kg Ht...............cm. BSA...................m
() .................................
Histology
Embryonal CNS tumors
Medulloblastoma/supratentorial PNET Atypical/rhabdoid teratoid tumor
Pineloblastoma Ependymoblastoma
History
Physical examination
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
CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 179
Thai Pediatric Oncology Group
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
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 150 mg/m2 IV drip in 30 min once daily Day 1-3
*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
10
CNS Germ Cell Tumor: Treatment protocol for average risk medulloblastoma [ThaiPOG-BT-13-MB-AVR] 180
Thai Pediatric Oncology Group
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
CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR] 181
Thai Pediatric Oncology Group
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
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 150 mg/m2 IV drip in 30 min once daily Day 1-3
*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
10
CNS Germ Cell Tumor: Treatment protocol for high risk medulloblastoma [ThaiPOG-BT-13-MB-HR] 182
Thai Pediatric Oncology Group
Infant Brain Tumors (Age < 3 years old)
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
() .................................
Histology
Infant Brain Tumors (Age < 3 years old): Data entry form 183
Thai Pediatric Oncology Group
Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 184
Thai Pediatric Oncology Group
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
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.
Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 185
Thai Pediatric Oncology Group
Patients name.................................................................... Sex................... HN...........................................
Age (yy/mm).............................. BW...........................kg Ht...............................cm BSA.........................m2
Infant Brain Tumors (Age < 3 years old): Treatment protocol for infant brain tumors [ThaiPOG-BT-13-IFB] 186
Thai Pediatric Oncology Group
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
-If age above 18 months but less than 24 months,
M0; CSI 12 Gy with boost at posterior fossa or tumor bed 54-60 Gy
M+; CSI 18 Gy with boost at posterior fossa or tumor bed 54-60 Gy
-If age above 24 months but less than 36 months,
M0; CSI 18 Gy with boost at posterior fossa or tumor bed 54-60 Gy
M+; CSI 24 Gy with boost at posterior fossa or tumor bed 54-60 Gy
-If age above 36 months,
M0; CSI 24 Gy with boost at posterior fossa or tumor bed 54-60 Gy
M+; CSI 36 Gy with boost at posterior fossa or tumor bed 54-60 Gy
2. For ependymoma
-Focal irradiation 54-60 Gy
Infant Brain Tumors (Age < 3 years old): Irradiation guideline 187
Thai Pediatric Oncology Group
Infant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline 188
Thai Pediatric Oncology Group
Leucovorin rescue guideline
Excretion 24 H MTX level 48 H MTX level 72 H MTX level Leucovorin rescue
/Toxicity
Expected =< 10 uM < 1 uM < 0.1 uM Maintain hydration at 125 ml/m2/h
excretion 15 mg/m2 q 6 H PO/IV until MTX level
< 0.1 uM
Grade I 0.1-0.49 uM Maintain hydration at 125 ml/m2/h
Mild-Delayed 15 mg/m2 q 6 H PO/IV until MTX level
excretion < 0.1 uM
Recheck MTX level/Cr q 24 H;
discontinue leucovorin when MTX level
< 0.1 uM
Grade I 11-49 uM 1-4.9 uM 0.5-4.9 uM Increase hydration to 200 ml/m2/h
Mild toxicity and/or and/or and/or 15 mg/m2 q 6 H PO/IV until MTX level <
25-50% increase 25-50% increase 25-50% increase 0.1 uM
Cr Cr Cr Recheck MTX level/ Cr q 24 H;
and/or and/or and/or discontinue leucovorin when MTX level
Grade I-II Grade I-II Grade I-II < 0.1 uM or normalized Cr or resolved
stomatitis stomatitis stomatitis mucositis
Grade II 11-49 uM 1-4.9 uM 0.5-4.9 uM Increase hydration to 200 ml/m2/h
Moderate toxicity and/or and/or and/or 15 mg/m2 q 3 H IV until MTX level < 0.1
50-100% increase 50-100% increase 50-100% increase uM
Cr Cr Cr Recheck MTX level/ Cr q 24 H;
and/or and/or and/or discontinue leucovorin when MTX level
On previous or On previous or On previous or < 0.1 uM or normalized Cr or resolved
current course of current course of current course of mucositis
HD MTX: Grade HD MTX: Grade HD MTX: Grade
III-IV stomatitis, III-IV stomatitis, III-IV stomatitis,
myelosupression myelosupression myelosupression
Grade III 50-499 uM 5-99 uM 5-49 uM Increase hydration to 200 ml/m2/h
Severe Toxicity and/or and/or and/or 150 mg/m2 q 3 H IV until MTX level
>100% increase >100% increase >100% increase < 0.1 uM
Cr Cr Cr Recheck MTX level/ Cr q 24 H;
discontinue leucovorin when MTX level
< 0.1 uM or normalized Cr or resolved
mucositis
Nephrology consultation
Grade IV >= 500 uM >= 100 uM >= 50 uM Increase hydration to 200 ml/m2/h
Life threatening 1,500 mg/m2 q 3 H IV until MTX level <
0.1 uM
Recheck MTX level/ Cr q 24 H;
discontinue leucovorin when MTX level
< 0.1 uM
Nephrology consultation
Infant Brain Tumors (Age < 3 years old): High dose methotrexate infusion guideline 189
Thai Pediatric Oncology Group
Neuroblastoma
International neuroblastoma risk group (INRG) staging system
Stage Description
L1 Localized tumor not involving vital structures as defined by the list of image-defined risk factors and
confined to one body compartment
L2 Locoregional tumor with presence of one or more image-defined risk factors
M Distant metastatic disease (except stage MS)
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
Schematic treatment
Protocol for very low/ low risk neuroblastoma
(ThaiPOG-NB-13-LR)
Stage MS Non-stage MS
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%
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.
Induction Chemotherapy
Induction Agent (s) Dose (s)
Cycle 1,2 Topotecan 1.2 mg/m2 IV on daily Day 1-5
Cyclophosphamide >12 kg 400 mg/m2 IV once daily Day 1-5
12 kg 13.3 mg/kg IV once daily Day 1-5
Cycle 3,5 Cisplatin >12 kg 50 mg/m2 IV once daily Day 1-4
12 kg 1.66 mg/kg IV once daily Day 1-4
Etoposide >12 kg 200 mg/m2 IV once daily Day 1-3
12 kg 6.67 mg/kg IV once daily Day 1-3
Cycle 4,6 Cyclophoshamide >12 kg 2,100 mg/m2 IV once daily Day 1,2
12 kg 70 mg/kg IV once daily Day 1,2
Doxorubicin >12 kg 25 mg/m2 IV once daily Day 1-3
12 kg 0.83 mg/kg IV once daily Day 1-3
Vincristine >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.
Neuroblastoma: Treatment protocol for low risk neuroblastoma [ThaiPOG- NB-13-LR] 197
Thai Pediatric Oncology Group
Neuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR] 198
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
* Total daily mesna dose to be equal to (100% of) the daily cyclophosphamide dose
Assess treatment response, and perform surgery if residual primary tumor detected
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for standard risk neuroblastoma [ThaiPOG- NB-13-SR] 199
Thai Pediatric Oncology Group
Induction I
Given dose/day Drug Dosage
..........................mg Topotecan 1.2 mg/m2 IV once daily Day 1-5
..........................mg Cyclophosphamide >12 kg 400 mg/m2 IV once daily Day 1-5
12 kg 13.3 mg/kg IV once daily Day 1-5
........................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*
Days 1 2 3 4 5 1 2 3 4 5
Topotecan
Cyclophosphamide
Cycle Cycle day Treatment Date given Remarks
1 Cyclophosphamide/ Topotecan NSE/VMA
2 Cyclophosphamide / Topotecan
1 3 Cyclophosphamide / Topotecan
4 Cyclophosphamide / Topotecan
5 Cyclophosphamide / Topotecan
1 Cyclophosphamide / Topotecan NSE/VMA
2 Cyclophosphamide / Topotecan
2* 3 Cyclophosphamide / Topotecan
4 Cyclophosphamide / Topotecan
5 Cyclophosphamide / Topotecan
*To give GCSF at 10 mcg/kg/day after cycle 2 if plan to collect stem cells (frozen)
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
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Induction II
Given dose/day Drug Dosage
...................................mg Cisplatin >12 kg 50 mg/m2 IV once daily Day 1-4
12 kg 1.66 mg/kg IV once daily Day 1-4
...................................mg Etoposide >12 kg 200 mg/m2 IV once daily Day 1-3
12 kg 6.67 mg/kg IV once daily Day 1-3
...................................mg Cyclophoshamide** >12 kg 2,100 mg/m2 IV once daily Day 1-2
12 kg 70 mg/kg IV once daily Day 1-2
...................................mg Doxorubicin >12 kg 25 mg/m2 IV once daily Day 1-3
12 kg 0.83 mg/kg IV once daily Day 1-3
...................................mg Vincristine >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
...................................mg Mesna** 420 mg/m2 (or 14 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 3 4 5 6*
Day 1 2 3 4 1 2 3 1 2 3 4 1 2 3
Cisplatin
Etoposide
Cyclophoshamide
Doxorubicin
Vincristine
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 201
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Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Induction II (continue)
Date
Cycle Cycle day Treatment Remarks
given
1 Cisplatin/Etoposide NSE/VMA
2 Cisplatin/Etoposide
3
3 Cisplatin/Etoposide
4 Cisplatin
1 Cyclophosphamide**/ Doxorubicin/ Vincristine NSE/VMA
4 2 Cyclophosphamide**/ Doxorubicin/ Vincristine
3 Doxorubicin/ Vincristine
1 Cisplatin/Etoposide NSE/VMA
2 Cisplatin/Etoposide
5
3 Cisplatin/Etoposide
4 Cisplatin
1 Cyclophosphamide**/ Doxorubicin/ Vincristine NSE/VMA
6* 2 Cyclophosphamide**/ Doxorubicin/ Vincristine
3 Doxorubicin/ Vincristine
* 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
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
Evaluation treatment response
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 202
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 1 2 3 4
Carboplatin
Etoposide
Ifosfamide
Mesna
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 203
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Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
High Risk Neuroblastoma Treatment Plan (ThaiPOG-NB-13-HR) ICE (continue)
Cycle Cycle day Treatment Date given Remarks
1 Carboplatin NSE/VMA
2 Ifosfamide /Etoposide
1
3 Ifosfamide /Etoposide
4 Ifosfamide /Etoposide
1 Carboplatin NSE/VMA
2 Ifosfamide /Etoposide
2
3 Ifosfamide /Etoposide
4 Ifosfamide /Etoposide
3 1 Carboplatin NSE/VMA
2 Ifosfamide /Etoposide
3 Ifosfamide /Etoposide
4 Ifosfamide /Etoposide
4 1 Carboplatin NSE/VMA
2 Ifosfamide /Etoposide
3 Ifosfamide /Etoposide
4 Ifosfamide /Etoposide
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
Evaluation treatment response
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 204
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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 1 2 3 4 5
Topotecan
Cyclophosphamide
Cycle
Cycle Treatment Date given Remarks
day
1 Cyclophosphamide/Topotecan NSE/VMA
2 Cyclophosphamide/Topotecan
1 3 Cyclophosphamide/Topotecan
4 Cyclophosphamide/Topotecan
5 Cyclophosphamide/Topotecan
1 Cyclophosphamide/Topotecan NSE/VMA
2 Cyclophosphamide/Topotecan
2 3 Cyclophosphamide/Topotecan
4 Cyclophosphamide/Topotecan
5 Cyclophosphamide/Topotecan
1 Cyclophosphamide/Topotecan NSE/VMA
2 Cyclophosphamide/Topotecan
3 3 Cyclophosphamide/Topotecan
4 Cyclophosphamide/Topotecan
5 Cyclophosphamide/Topotecan
Evaluation treatment response
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 205
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
Cycle Treatment Date given Remarks
week
1-2 13-cis-retinoic acid NSE/VMA
1
3-4 Off
5-6 13-cis-retinoic acid
2
7-8 Off
3 9-10 13-cis-retinoic acid NSE/VMA
11-12 Off
13-14 13-cis-retinoic acid
4
15-16 Off
17-18 13-cis-retinoic acid NSE/VMA
5
19-20 Off
6 21-22 13-cis-retinoic acid
Evaluation treatment response
CT /MRI (//) .....
Bone scan (//) .........
Bone marrow examination (//)..............
MIBG (//) ......
NSE/VMA (//)
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 206
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Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Haploidentical donor HSCT (following HD-MIBG) recommended regimen
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 207
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Matched-related donor HSCT (following HD-MIBG) recommended regimen
Day Treatment Date given Remarks
2
-6 Busulfan 37.5 mg/m /dose IV every 6 hr
-5 Busulfan 37.5 mg/m2/dose IV every 6 hr
-4 Busulfan 37.5 mg/m2/dose IV every 6 hr
-3 Busulfan 37.5 mg/m2/dose IV every 6 hr
Melphalan 70 mg/m2/day IV
-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
until ANC > 2,000/mm3 x 2 SQ
* MMF started from day 0
Cyclosporine started from day -2
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 208
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Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Autologous HSCT (following HD-MIBG) recommended regimen
Day Treatment Date given Remarks
2
-6 Busulfan 37.5 mg/m /dose IV every 6 hr
-5 Busulfan 37.5 mg/m2/dose IV every 6 hr
-4 Busulfan 37.5 mg/m2/dose IV every 6 hr
-3 Busulfan 37.5 mg/m2/dose IV every 6 hr
-2 Melphalan 70 mg/m2/day IV
-1 Melphalan 70 mg/m2/day IV
0 HSC Infusion
GCSF 5 mcg/kg/day
+5
until ANC > 2,000/mm3 x 2 SQ
Neuroblastoma: Treatment protocol for high risk neuroblastoma [ThaiPOG- NB-13-HR] 209
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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.)
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.
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
Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 213
Thai Pediatric Oncology Group
Schematic treatment for intraocular retinoblastoma
Unilateral retinoblastoma
Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 214
Thai Pediatric Oncology Group
Schematic treatment for extraocular retinoblastoma
Extraocular retinoblastoma
Retinoblastoma: Summary treatment strategy based on laterality and retinoblastoma grouping 215
Thai Pediatric Oncology Group
Post-treatment evaluation
For patients with preserved eye
Evaluation Schedule Note
Eye examination under - Every 3-4 weeks until no active tumor on minimum 3 Patients should be
anesthesia (EUA) EUAs examined without
-Then every 6-8 weeks until 3 years of age anesthesia when old
-Then every 4-6 months until 10 years of age enough to cooperate.
-Then yearly
MRI brain and orbit -Every 6-12 months until 5 years of age
For patients after enucleation and/or received EBRT
Evaluation Schedule Note
Eye examination under -At 4-6 weeks post treatment Patients should be
anesthesia (EUA) -Then every 2-3 months in year 1 examined without
-Then every 3-4 months in year 2 anesthesia when old
-Then every 6 months until 5 years of age enough to cooperate.
-Then yearly
For patients with extraocular disease
Evaluation Schedule Note
CT or MRI of the brain and Every 6 months in first 3 years then every year until 5 - prefer MRI to avoid
orbits years after off treatment radiation exposure
CSF profiles and cytology 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
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 Every 6 months from the end of treatment until 5 years - Screen for trilateral
orbits of age retinoblastoma
- prefer MRI to avoid
radiation exposure
For patients who received chemotherapy and/or radiation therapy
Evaluation Schedule Note
History and physical -Every 3 months until 2 years off treatment - Late effects of treatment
examination -Then every 6 months until 5 years off - Growth and development
treatment - Surveillance for second malignant
-Then yearly neoplasms (osteosarcoma, soft tissue
sarcomas, skin cancers, breast
cancers)
Visual acuity assessment -Yearly
CBC -Yearly for 10-15 years from exposure of -Surveillance for secondary leukemia
chemotherapy
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
Inclusion criteria
Retinoblastoma ICRB group D
Retinoblastoma ICRB group E
10
11
12
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
Chemotherapy schedule
Week 0 3 6 9 12 15 18 21
Course A1 B1 A2 B2 A3 B3 A4 B4
Date
***** Start G-CSF at 24 -48 hr after completion each course of chemotherapy *****
Course A
Given dose Drug Dosage Day
__________mg Vincristine 0.05 mg/kg or 1.5 mg/m2 IV slowly push 1
__________mg Idarubicin 0.33 mg/kg or 10 mg/m2 IV infusion in 60 min 1
__________mg Cyclophosphamide* 65 mg/kg or 2,000 mg/m2 IV drip in 30-60 min 1
__________mg Mesna 30 mg/kg or 1,000 mg/m2 IV drip in in15 min 1
at 0,3 hr after CTX (total 2 doses)
In patient BW < 12 kg, use doses per kg
* hydration following High dose CTX guideline
Course B
Given dose Drug Dosage Day
__________mg Etoposide 3.3 mg/kg or 100 mg/m2 IV drip in 60 min 1-3
__________mg Carboplatin 18.6 mg/kg or 560 mg/m2 IV drip in 15-30 min 1-2
In patient BW < 12 kg, use doses per kg
A1
B1
A2
B2
A3
B3
A4
B4
Inclusion criteria
Retinoblastoma with CNS/ bone/ bone marrow involvement
Retinoblastoma with isolated meningeal disease
Ectopic intracranial retinoblastoma
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) ..........
* Use the same imaging modality CT or MRI for all disease evaluations.
Dosage
Drug
Age < 12 months Age 12 months BW 30 kg
AMD = Actinomycin-D X 1day 0.023 mg/kg IV 0.045 mg/kg IV 1.35 mg/M2 IV
(Maximum dose 2.3 mg)
VCR1 = Vincristine X 1day 0.025 mg/kg IV 0.05 mg/kg IV 1.5 mg/M2 IV
(Maximum dose 2 mg)
VCR2 = Vincrintine X 1day 0.034 mg/kg IV 0.067 mg/kg IV 2 mg/M2 IV
(Maximum dose 2 mg)
B. Imaging study
CT chest (//) ....
.
Chest X-Ray (//) ...
CT/ MRI abdomen* (//) .........
* Use the same imaging modality CT or MRI for all disease evaluations.
B. Imaging study
CT chest (//) ......
..
Chest X-Ray (//) .......
Abdominal Ultra Sound (//) .....
CT/ MRI abdomen* (//) ...........
EKG/ECHO (//) .........
* Use the same imaging modality CT or MRI for all disease evaluations.
#at baseline abdominal US and Doppler recommended but not require excluding IVC tumor thrombus
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) .....
CT/ MRI abdomen* (//) .........
* Use the same imaging modality CT or MRI for all disease evaluations.
Dosage
Drug
Age < 12 months Age 12 months BW 30 kg
DOX = Doxorubicin X 1day 0.75 mg/kg IV 1.5 mg/kg IV 45 mg/M2 IV
VCR1 = Vincristine X 1day 0.025 mg/kg IV 0.05 mg/kg IV 1.5 mg/M2 IV
(Maximum dose 2 mg)
VCR2 = Vincrintine X 1day 0.034 mg/kg IV 0.067 mg/kg IV 2 mg/M2 IV
(Maximum dose 2 mg)
CTX5 = Cyclophophamide X 5 days 7.35 mg/kg/day 14.7 mg/kg/day 440 mg/M2/day
CTX3 = Cyclophophamide X 3 days
ETOP = Etoposide X 5 days 1.65 mg/kg/day 3.3 mg/kg/day 100 mg/M2/day
Week Date BSA DOX VCR1 VCR2 CTX5 CTX3 ETOP Note
0 *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
Evaluate: date (/....../..) CBC ......
BUN Creatinine Electrolyte..
LFT...
B. Imaging study
CT chest (//) ......
..
Chest X-Ray (//) .......
Abdominal Ultra Sound (//) .....
CT/ MRI abdomen* (//) ...........
EKG/ECHO (//) .........
* Use the same imaging modality CT or MRI for all disease evaluations.
#at baseline abdominal US and Doppler recommended but not require excluding IVC tumor thrombus
B. Imaging study
CT chest (//) .....
.
Chest X-Ray (//) ......
CT/ MRI abdomen* (//) .........
* Use the same imaging modality CT or MRI for all disease evaluations.
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
Pre-treatment Investigations
A. Imaging study
CT scan liver (___/___/___)
1. CDDP
electrolytes, Ca, Mg, BUN creatinine, U/A
k x Height cm
GFR Schwartz formula GFR (ml /min /1.73 m2) =
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
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
Post-treatment evaluation
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
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
Thai Pediatric Oncology Group
Protocol name ThaiPOG-HB-13-VLR
Protocol for Very low risk hepatoblastoma
Open date January 2014
Modified from 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)
Hepatoblastoma: Treatment summary for very low risk hepatoblastoma [ThaiPOG-HB-13-VLR] 250
Thai Pediatric Oncology Group
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. 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 anti-
emetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.
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
II ___/___/___
III ___/___/___
IV ___/___/___ *
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. 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, 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
7. 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 anti-
emetic in patient >12 year. Reduce Dexamethasone dose to 50% by half if Aprepitant was given.
1. First course of chemotherapy should be started within 7-14 days after the diagnosis
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
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
2. First course of chemotherapy should be started within 7-14 days after the diagnosis
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
Hepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 257
Thai Pediatric Oncology Group
Protocol name ThaiPOG-HB-13-VHR
Protocol for Very High risk hepatoblastoma
Open date January 2014
Reference COG AHEP0731 protocol, treatment regimen W
Patient eligibility
Patient with low AFP (< 100 ng/ml)
Anti-emetic guideline
___________ 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
Give chemotherapy q 3 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]
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
Hepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 258
Thai Pediatric Oncology Group
Patients name Age Sex HN
BW Ht BSA
ThaiPOG-HB-13-VHR protocol
Initial Biopsy no yes ( Date ___/___/___ ) section # ______________
result__________________________
liver
Course Date Regimen AFP Dose adjusted Hearing test
size
I ___/___/___ VI *
II ___/___/___ VI
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)
IV ___/___/___ C5VD
V* ___/___/___ VI*
VI ___/___/___ C5VD
IX ___/___/___ C5VD
X ___/___/___ C5VD
Hepatoblastoma: Treatment summary for very high risk hepatoblastoma [ThaiPOG-HB-13-VHR] 259
Thai Pediatric Oncology Group
Osteosarcoma
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 Physical examination
Inclusion criteria
Localized osteosarcoma
Cycle 1 2 3 4 5 6 7 8 9 10 11 12
Week 0 3 6 9 12 14 17 20 23 26 29 32 35 38
Date
I I I A* I I A I I A I A**
Induction Cb Cb Cb A Cb Cb A Cb Cb A** Cb
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
Surgery
Surgery date (//) Surgeon ...
Type of surgery: Amputation 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 (//) .....
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
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 264
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
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
3 10 (**)
13
14
Cumulative dose (mg/m2)
Surgery
Surgery date (//) Surgeon ...
Type of surgery: Amputation Limb salvage Rotationplasty
.
Tumor necrosis %
Surgical margin Adequate (> 5 cm) Inadequate (not free margin, margin < 5 cm.)
Evaluation
4. CT/ MRI .(//) .....
5. Bone scan (//) ......
6. CXR/CT scan chest (//) .....
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 265
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
2nd Audiogram (postoperative) Normal Sensorineural hearing loss
*Echocardiogram (postoperative) Normal Impaired ejection fraction . %
Phase II: Adjuvant I (If tumor necrosis 90%)
Cycle week Date BSA Cisplatin Doxorubicin MTX Note
60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day
4 15 (***)
18
19
Cumulative dose (mg/m2)
5 20 (**)
23
24
6 25 (**)
28
29
Phase II: Adjuvant II (tumor necrosis < 90%)
Cycle Week Date BSA Cisplatin Doxorubicin MTX Ifosfamide Note
60 mg/m2/day 37.5 mg/m2/day 12 gm/m2/day 2.4 gm/m2/day
4 15 (***)
18
19
5 20
23
24
6 25
28
29
7 30
*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
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 266
Thai Pediatric Oncology Group
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
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 = 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
6. Furosemide 0.5 mg/kg/dose can be used to increase urine volume
Osteosarcoma: Treatment protocol for localized (non-metastatic) osteosarcoma [ThaiPOG-OS-13- MTX] 267
Thai Pediatric Oncology Group
Inclusion criteria
Metastatic osteosarcoma
Week 1 4 5 6 9 10 11 12 15 16 19 20 23 24 27 28 31 32 35 36 39 40
Date
A M M A M M A M I M A M I M A** M I M A** M M
Induction P P P E I* E P E I*
Evaluation (1) (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
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 IV drip in 1 hour OD x 5 days
Mesna 600 mg/m /dose IV at 0, 3rd, 6th, 9th hour after Ifosfamide
2
Surgery
Surgery date (//) Surgeon ...
Type of surgery: Amputation Limb salvage Rotationplasty
.
Tumor necrosis %
Surgical margin Adequate (> 5 cm) Inadequate (not free margin, margin < 5 cm.)
Evaluation
7. CT/ MRI .(//) .....
8. Bone scan (//) ......
9. CXR/CT scan chest (//) .....
*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
Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 273
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
Wk Cycle date BW HT BSA Drug Calculated Dose with BSA
Surgery (tumor removal) date of...../....../....... .
12
Adequate margin ( no need for radiation) Inadequate margin (need radiation at primary site)*
VCR 2 mg/ m2 = ............................................................mg
VDC
CTX 1,200 mg/ m2 = ... mg with Mesna
With
14 7 ...../....../........ Doxo 37.5 mg/ m2 /day (x2day) = .................................mg
*start
day1.....................................................................................
radiation
day2 ................................................................................
Ifosphamide 1,800 mg/ m2 /day Etoposide 100 mg/ m2/day
(x5day) =..mg (x5day) =..mg
day1.... day1...
16 8 ...../....../........ IE day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
CTX 1,200 mg/ m2 = ... mg with Mesna
18 9 ...../....../........ VDC 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...
20 10 ...../....../........ IE day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
22 11 ...../....../........ VC
CTX 1,200 mg/ m2 = ... mg with Mesna
Ifosphamide 1,800 mg/ m2 /day Etoposide 100 mg/ m2/day
(x5day) =..mg (x5day) =..mg
day1.... day1...
24 12 ...../....../........ IE day2 day2...
day3 day3.......
day4 day4
day5....... day5........
VCR 2 mg/ m2 = ............................................................mg
26 13 ...../....../........ VC
CTX 1,200 mg/ m2 = ... mg with Mesna
Ifosphamide 1,800 mg/ m2 /day Etoposide 100 mg/ m2/day
(x5day) =..mg (x5day) =..mg
day1.... day1...
28 14 ...../....../........ IE day2 day2...
day3 day3.......
day4 day4
day5....... day5........
Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 274
Thai Pediatric Oncology Group
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
Ewing Sarcoma Family of Tumors: Treatment protocol for Ewing sarcoma [ThaiPOG-EWS-13-SR] 275
Thai Pediatric Oncology Group
2. Chest: CT non-contrast
Every 3-6 months x 2 years,
Every 6-12 months x 3 years,
Every 12 months x 5 years
AP and lateral radiographs Every 12 months x 5 years after last CT
Ewing Sarcoma Family of Tumors: Follow up schedule after complete treatment 276
Thai Pediatric Oncology Group
Consult cardiologist for 2D-Echocardiogram when accumulative dose of doxorubicin > 300 mg / m2 or
when > 200 mg / m2 in infant
Ewing Sarcoma Family of Tumors: Guideline for administration of high dose cyclophosphamide/ 278
ifosfamide
Thai Pediatric Oncology Group
Rhabdomyosarcoma
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 Physical examination
Post-treatment evaluation
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.
Cycle 1 2 3 4 5 6 7 8
Week 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Evaluation
Chemo V V 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 A A
C C C C - - - -
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 Dosage Total dose
V: Vincristine 1.5 mg/m2 /day IV push slowly (maximum dose, 2 mg)
A: Dactinomycin* 0.045 mg/kg/day IV push slowly (maximum dose, 2 mg)
C: Cyclophosphamide 1.2 gm/m2/dose IV drip in 1 hr x 1 day
Evaluation
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
3. CXR/CT scan chest (//) .....
Radiotherapy
Radiotherapy date (//) Total dose (Gy): .
Technique: .. Involved field: .
Evaluation
4. CT/ MRI .(//) .....
5. Bone scan (//) ......
6. CXR/CT scan chest (//) .....
Evaluation (1)
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
3. CXR/CT scan chest (//) .....
Radiotherapy
Radiotherapy date (//) 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 (3)
1. CT/ MRI .(//) .....
2. Bone scan (//) ......
3. CXR/CT scan chest (//) .....
Germ Cell Tumor: Staging of germ cell tumor (gonadal and extragonadal) 293
Thai Pediatric Oncology Group
gonadal and extragonadal germ cell tumor
Evaluation
Complete Partial
response response
Off Second
treatment look surgery
Germ Cell Tumor: gonadal and extragonadal germ cell tumor 294
Thai Pediatric Oncology Group
PEB JEB
Regimen Bleomycin Etoposide Cisplatin Carboplatin
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 , 600 mg/ m2,
(every 21-28 days)* day 1 day 1-3 day 2
* JEB PEB cisplatinum
Germ Cell Tumor: Type of germ cell tumor by staging and by risk group 295
Thai Pediatric Oncology Group
Physical examination
Primary Site and Size Metastatic Site
Diagnosis Stage
surgery
V
VI
Germ Cell Tumor: Treatment protocol for germ cell tumor [ThaiPOG-GCT-13] 297
Thai Pediatric Oncology Group
Patients name..................................................................... Sex........................... HN...........................................
Age (yy/mm)................................ BW............................. kg. Ht.............................cm BSA..............................m2
cisplatinum (CDDP)
1. CDDP
electrolytes, Ca, Mg, BUN creatinine, U/A
0.55 x Ht cm
GFR GFR ml/ min/ 1.73 sqm
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)
Tumor marker: AFP and / or HCG 1-2 6 3
CT or MRI tumor primary site 4 6
cisplatin 4-6
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
GR PR/NR PD
Off protocol
Induction-II
Paliative vs HSCT
GR/PR NR/PD
NR/PD
GR/PR
Continuation Salvage
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 ___________________________________________________
Week 1 2 3 4 5 6
Day 1 8 15 22 29 36
Date given
Prednisolone __________ taper off
Vinblastine ____________ mg
Week 1 2 3 4 5 6
Day 1 8 15 22 29 36
Date given
Prednisolone __________ III III III III III III
Vinblastine ____________ mg
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 Cycle Date Note
BSA:_______VBL: _______Pred: _______6-MP: _______ BSA:_______VBL: _______Pred: _______6-MP: _______
1 11
Note:
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
Hemophagocytic lymphohistiocytosis
History
Fever Abdominal mass Other specified:.
Bleeding CNS symptoms Anemia
Physical Examination
Fever Anemia Other specified:.
Hepatomegaly CNS abnormalities Splenomegaly
Lymphadenopathy Bleeding evidences
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 _____________________
IVIG ____________ mg
CSA________ml** q12hr ____ ml ____ ml ____ ml ____ ml ___ ml ____ ml ____ ml ____ ml
IT# T# T# T# T#
*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 6 8 10 12
Hydrocortisone 4 6 8 10
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 (____/____/____)