Acute Lymphoblastic

Leukemia in Pediatrics
Ibrahim Al-Ghemlas
Consultant, Pediatric Hematology/ Oncology @
KFSH&RC
Assistant Professor @ Alfaisal University
What is childhood leukemia?

 Leukemia is a cancer that starts in early blood-

forming cells.
 Any of the cells from the bone marrow can turn
into a leukemia cell.
 The leukemia cells don’t go through the normal
process of maturing.
 They survive and build up in the bone marrow,
crowding out normal cells.
 In most cases, the leukemia cells spill into the
bloodstream fairly quickly and can go to other
parts of the body (infiltration).
Incidence

 Leukemia is the most

common cancer in children
and teens, accounting for
almost 1 out of 3 cancers
(~31%).

 1 case in 20000 each year

 Around 1000 cases of

Leukemia in Saudi Arabia per
year.
Normal bone marrow, blood,
and lymphoid tissue
Types of Acute leukemia
 Acute lymphocytic (lymphoblastic) leukemia (ALL):
 About 3 out of 4 cases of childhood leukemia (75-80%).
 Starts from the lymphoid cells in the bone marrow.

 Acute myelogenous (myeloid) leukemia (AML):

 Accounts for most of the remaining cases (20-25%).
 AML starts from the myeloid cells that form white blood cells
(other than lymphocytes), red blood cells, or platelets.

 Mixed lineage leukemia (biphenotypic):

 A rare leukemia, the cells have features of both ALL and AML.
 In children, they are generally treated like ALL and respond to
treatment like ALL.
Blood film in patient with ALL
BMA in patient with ALL
BMA in patient with ALL
BMA in patient with AML
Do we know what causes childhood
leukemia?

 The exact cause of most cases of childhood leukemia is

not known.
 Most children with Leukemia do not have any known risk
factors.
Signs and symptoms
 Fatigue, pale skin  Swollen lymph nodes

 Infections and fever  Coughing or trouble breathing

 Easy bleeding or bruising  Swelling of the face and arms

 Bone or joint pain  Headache, seizures, vomiting

 Swelling of the abdomen  Chloroma or granulocytic

sarcoma

 Loss of appetite, weight loss

Diagnosis
Diagnosis

 Lab tests used to diagnose and classify

leukemia
 Routine microscopic exams
 Cytochemistry
 Flow cytometry and immunohistochemistry
 Cytogenetics
 Fluorescent in situ hybridization (FISH)
 Polymerase chain reaction (PCR)
Case presentation

 13 years old male, previously well

 1 week history of fatigue, 2 days of fever

 Physical exam:
 Pale, tachycardia HR 110, febrile 38.5c, BP stable
 Cervical adenopathy, HSM
 Chest clear
 No bruising or petechiae
Case presentation

 Hematology:
 HB: 54 G/L
 Platelets: 77
 WBC: 135.5
 ANC: 1.5
 K: 3.5 BUN: 4 Crea: 56 Uric Acid: 360
 Ca: 1.2 PO4: 1.2

 CXR: normal
Case presentation

 Started on allopurinol , Hydration at twice maintenance

, alkalinization, broad spectrum antibiotics

 Diagnosed as ALL

 Started on induction chemotherapy

Case presentation

Following initiation of chemotherapy:

 K : 3.2  4.4 5.1  5.8
 Ca: 1.12  1.0  0.8  0.6
 PO4: 1.2  1.6  2.4  3
 Crea : 56  92.  101  134  180
 urine out put < 1 cc/kg/hr
 Hypertensive
Tumor lysis Syndrome

 An oncologic emergency that is caused by massive

tumor cell lysis with the release of large amounts of
potassium, phosphate, and nucleic acids into the
systemic circulation.

 Hyperuricemia , hyperkalemia , hyperphosphatemia ,

hypocalcemia

 Hyperuricemia can result in intrarenal precipitation of

urate or xanthines
Tumor lysis Syndrome

 Laboratory TLS is defined as any two or more of the

following metabolic abnormalities and presents within
three days before or seven days after instituting
chemotherapy: hyperuricemia, hyperkalemia,
hyperphosphatemia, and hypocalcemia.

 Clinical TLS is defined as laboratory TLS plus one or

more of the following that was not directly or probably
attributable to a therapeutic agent: increased serum
creatinine concentration (≥1.5 times the ULN), cardiac
arrhythmia/sudden death, or a seizure.
Tumor lysis Syndrome

 Use of allopurinol (xanthine oxidase inhibitor) prevents

uric acid synthesis and urate nephropathy
 Rasburicase is (urate oxidase agonist)
 Alkalinization promotes solubility
 Hydration decreases urinary concentration
 Hyperphosphatemia can result in intratubular deposition
of phosphate , hypocalcemia and precipitation of Ca -
PO4 saults,
 Treat with Amphogel
Prognostic factors in childhood
leukemia

Prognostic factors for children with ALL

 Age at diagnosis:
 1-10 years is good factor
 <1 year or >10 years is high risk factor
 WBC) count:
 Children with high WBC counts (> 50,000) are classified as
high risk
 Subtype of ALL:
 pre-B or early pre-B-cell ALL generally do better than
mature B-cell leukemia.
 T-cell ALL need intensified treatment.
Prognostic factors in childhood
leukemia

 Spread to certain organs:

 Spread of the leukemia into the CSF, or the testicles in
boys, increases the chance of a poor outcome
 Number of chromosomes:
 leukemia cells have more than 50 chromosomes
(hyperdiploidy), especially if there is an extra
chromosome 4, 10, or 17 is a favorable factor .
 leukemia cells have fewer chromosomes than the normal
46 (hypodiploidy) have a less favorable outlook.
Prognostic factors in childhood
leukemia

 Chromosome translocations:
 Translocations result when DNA is swapped between
chromosomes.
 Children whose leukemia cells have a t12-21 are more
likely to be cured.
 Those with a t9- 22 (the Philadelphia chromosome), t1-19,
or t4-11 tend to have a less favorable prognosis.
 Response to treatment:
 Children whose have remission within 1 to 2 weeks of
chemotherapy have a better outcome
 Children whose cancer does not respond well may be given
more intensive chemotherapy.
B-cell ALL classification
 Low risk
 Patients should have all of the following features:
 Age >1 year and <10 years
 WBC count <50K
 CNS negative (CNS1)
 No testicular disease
 Triple trisomy (trisomy of chromosomes 4, 10 and 17)
OR
 TEL-AML1 fusion [t(12;21)]
 No adverse cytogenetics
 All these patients should have Day 14 <5% blasts (rapid
responder)
B-cell ALL classification
 High risk
 Patients with any one of the following would be
considered HR:
 Age > 10 years
 WBC count > 50K
 CNS 2 status
 Testicular disease
 E2A-PBX1fusion or t(1;19)
 All these patients should have Day 14 <5% blasts (rapid
responder)
B-cell ALL classification

 Very high risk

 CNS disease (CNS 3)
 DNA index <0.8
 Non infants with MLL gene rearrangement
 Patients with a t9- 22 (the Philadelphia chromosome)
 All patients were on LR or HR protocols with Day 14 >5%
blast (slow responder)
T-cell ALL classification

 Low risk
 WBC count <50K
 CNS negative

 High risk
 WBC count >50K
 CNS positive
Central line Insertion
Chemotherapy for Childhood
Leukemia
 The treatment of leukemia uses combinations of several
chemo drugs.

 We give chemo in cycles, with each period of treatment

followed by a rest period to give the body time to
recover.

 In general, treatment for AML uses higher doses of

chemo over a shorter period of time, and ALL
treatment uses lower doses of chemo over a longer
period of time (usually 2 to 3 years).
Chemotherapy for Childhood
Leukemia
 Vincristine (IV)  6-thioguanine (PO)
 Daunorubicin (IV)  Methotrexate (PO /IV)
 Doxorubicin (IV)  Mitoxantrone IV)
 Cytarabine (IV)  Cyclophosphamide (IV)
 L-asparaginase (IM or  Prednisone (PO)
IV)
 Dexamethasone (PO/IV)
 Etoposide (IV)
 6-mercaptopurine (PO)
Side Effects of Chemo
 The side effects of chemo depend on the type and
dose of drugs given and the length of time they
are taken.
 These side effects may include:
 Hair loss
 Mouth sores
 Loss of appetite
 Diarrhea
 Nausea and vomiting
 Increased risk of infections (because of low white
blood cell counts)
 Bruising and bleeding easily (from low platelet
counts)
 Fatigue (caused by low red blood cell counts)
Treatment of children with ALL

 The main treatment for children with acute lymphocytic

leukemia (ALL) is chemotherapy, which is usually divided
into 3 phases:
 Induction (1 month)
 Vincristine, Steroid, L-asparaginase (LR induction)
 Vincristine, Steroid, L-asparaginase, Doxorubicin (HR induction)

 Consolidation and re-intensification) ( 3-6 months)

 Maintenance ( 2 years for girls and 3 years for boys)

 Vincristine (IV), 6-mercaptopurine (PO), Methotrexate (PO),
Steroid (PO).
High-dose chemotherapy and
stem cell transplant

 Poor response to chemotherapy in patient with ALL

 Early relapsed ALL
Survival rates for childhood
leukemia
 The 5-year survival rate for children with ALL has
greatly increased over time and is now more than
85% overall.

 The overall 5-year survival rate for children with

AML has also increased over time, and is now in
the range of 60% to 70%.
THANK YOU