• Unknown

• Exposure to ionizing radiation
• Chemical exposure
• Viral infections
  • HTLV I associated with adult T cell leukemia
  • HTLV II associated with hairy cell leukemia

• Immunodeficiencies
  • Wiskott-Aldrich syndrome
  • Ataxia telangiectasia
  • Congenital hypogammaglobinemia
  • Prolonged immunosuppressive therapy is related to lymphoid malignancies

• Bone marrow aspirate shows >30% leukemic lymphoblasts
• French American British (FAB) Classification: based on morphology
• Immunologic Classification
  • B cell lineage
    • 80% to 85% of childhood cases, mostly early pre-B cell or pre-B cell
    • Pre-B and early pre-B cell usually common
• ALL antigen (CALLA) positive
  • Immunological markers for B cell lineage are CD19, CD20, CD21, and CD24
  • T cell lineage
    • 15% to 20% of all cases
    • 10% of these are CALLA positive
    • Immunological markers for T cell lineage are CD1, CD2, CD3, CD4, CD5, CD7, and CD8
• Cytochemistry
  • ALL blasts usually periodic acid-Schiff (PAS) positive
  • Always negative for Sudan black and Myeloperoxidase
• Cytogenetics
  • Karyotype of malignant cells is normal in 50% of cases
  • Others have several translocations
    • t (4;11) associated with infant ALL
    • t (1;19), t (9;22) Philadelphia chromosome
    • t (11;18) associated with T cell disease
    • t (8;14) associated with B cell disease
  • Hyperdiploid (> 50 chromosomes) state associated with good prognosis

• Trisomy 21
• Fanconi anemia
• Bloom syndrome
• Ataxia telangiectasia
• Klinefelter syndrome
• Schwachmann Diamond syndrome
• 20% risk of ALL in monozygotic twin if one twin develops ALL before 5 years of age
• 2- to 4-fold higher risk in siblings than in general population

• Acute leukemia is most common cancer of childhood
• Incidence of ALL is 4/100,000 children younger than 5 years old
• >75% of acute leukemia in childhood is ALL
• Peak incidence at 4 years of age
• More common in whites and boys
• Higher incidence in industrialized countries

• Due to disease:
  • Failure of remission induction—uncommon
  • Central nervous system (CNS) relapse
  • Testicular relapse
  • Bone marrow relapse
  • Infections, sepsis, and hemorrhage

• Due to therapy:
  • Cranial radiation (XRT) and intrathecal methotrexate (IT MTX)
    • Leukoencephalopathy and deterioration of intellectual functions
    • Growth retardation
  • Prednisone
    • Avascular necrosis of bones
    • Cushingoid habitus
    • Hypertension
  • Vincristine (VCR)
    • Syndrome of inappropriate antidiuretic hormone
    • Footdrop (reversible)
    • Hair loss
  • L-asparaginase
    • Pancreatitis
    • Coagulopathy leading to cerebral infarcts
  • Adriamycin
    • Cardiac toxicity
  • Cyclophosphamide
    • Hemorrhagic cystitis
    • Sterility
  • Methotrexate (MTX)
    • Hepatotoxicity

• Long-term survival in standard risk group is about 70% (>5 years after completion of therapy).
• Long-term survival is about 60% to 65% for high-risk group.

• Juvenile rheumatoid arthritis
• Infectious mononucleosis
• Idiopathic thrombocytopenic purpura
• Pertussis and parapertussis
• Aplastic anemia

• Neuroblastoma
• Lymphoma
• Rhabdomyosarcoma
• Retinoblastoma
• Acute myeloid leukemia

Question: Fever
Significance: Infection

Question: Bleeding (cutaneous and mucosal)
Significance: Low platelet count, coagulopathy

Question: Bone pains; Arthralgia, limp
Significance: Infiltrative disease of marrow

Question: Fatigue and pallor
Significance: Anemia

Question: Lymphnode enlargement
Significance: Infiltration with leukemia

Question: Stridor, orthopnea, shortness of breath
Significance: Mediastinal mass

Question: Oliguria
Significance: Renal failure

• Headache, vomiting, seizures

Finding: Pallor
Significance: Anemia

Finding: Lymphadenopathy (generalized)
Significance: Infiltration with leukemia

Finding: Hepatosplenomegaly
Significance: Infiltration with leukemia

Finding: Sternal tenderness
Significance: Bone marrow infiltration

Finding: Petechiae and purpura
Significance: Thrombocytopenia

Finding: Subconjunctival and retinal hemorrhages
Significance: Thrombocytopenia

Finding: Testicular enlargement in boys
Significance: Testicular infiltration

Finding: Papilledema in CNS leukemia
Significance: Meningeal infiltration

Finding: Congestive heart failure
Significance: Severe anemia

Finding: Swelling of the face, orthopnea
Significance: Superior venacaval syndrome in presence of mediastinal mass

Test: CBC
Significance: Increased white blood count

• >10,000/mm³ in 50% cases
• >50,000/mm³ in 20% cases

Neutropenia (<500/mm³) common
Hb <10 g/dL in 80% cases
Thrombocytopenia (<100,000/mm³) in 75% cases

Test: Bone marrow aspirate
Significance: >25% leukemic lymphoblasts is diagnostic

Test: Immunophenotyping and cytogenetic studies on bone marrow aspirate
Significance: Prognostic

Test: Biochemical abnormalities
Significance: Tumor lysis syndrome

• Hyperuricemia
• Hyperphosphatemia
• Hypocalcemia
• Hyperkalemia
• Increased LDH
• Slight abnormality of liver function tests due to leukemic infiltrate

Test: Chest x-ray
Significance: 5% to 10% cases have mediastinal mass

Test: CSF examination with lymphoblasts
Significance: CNS leukemia (5% at diagnosis)

• Age <1 year or >10 years of age
• WBC count >50,000/mm³
• Mediastinal mass or other bulky disease
• T or mature B cell disease
• Translocations—t (9;22), t (4;11), t (1;19)
• Hypodiploidy (<46 chromosomes by karyotype)

• Standard risk or high risk
• Four phases of therapy
  • Induction
  • Consolidation
  • Delayed intensification
  • Maintenance

• Induction
  • To achieve remission (<5% blasts in bone marrow)
  • Usually with 3 or 4 drugs
    • VCR
    • Prednisone
    • L-asparaginase with or without doxorubicin
  • Intrathecal methotrexate

• Consolidation and CNS prophylaxis
  • To prevent CNS disease
  • Intrathecal MTX along with oral 6-mercaptopurine (6MP) and MTX in standard risk
  • Intrathecal MTX along with cranial radiation (1800 cGy), oral 6MP and MTX for high risk patients

• Delayed Intensification
  • To further decrease leukemic burden
  • VCR
  • Prednisone
  • L-asparaginase
  • Doxorubicin
  • Cyclophosphamide
  • Cytosine arabinoside (ARA-C)
  • 6 thioguanine (6TG)
  • Intrathecal MTX

• Maintenance
  • Daily oral 6MP
  • Weekly MTX and monthly pulses of VCR and Prednisone
  • Intrathecal MTX for 2.5 to 3 years

• CNS leukemia at diagnosis
  • Cranial radiation (2400 cGy)
  • Triple intrathecal (MTX, ARA-C, Hydrocortisone), in addition to therapy above.

• Bone marrow transplant to be considered for relapsed patients.

• Blood and platelet transfusions as required.
• Broad spectrum antibiotics for fever and neutropenia.
• Pneumocystis prophylaxis with Trimethoprim/Sulphamethoxyzole.
• Varicella zoster immune globulin prophylaxis within 72 hours of exposure to varicella.
• No live viral vaccine to anyone in household.
• No vaccination to the affected child while on therapy.

Q: Can the child on treatment for ALL go to school?
A: Yes.

Q: Will the hair fall out and child be sick for all 3 years on chemotherapy?
A: The hair usually falls out only in first 6 months. Most children feel well during the maintenance chemotherapy.

Q: Does the child need to be isolated from other children?
A: The child should be isolated from any child who has varicella or is obviously sick due to any other infection.

Q: What do we do if we skip one dose of maintenance chemotherapy?
A: Continue to take the medication as recommended. Skipping one dose does not increase risk of relapse. However, missing doses should not become a habit.

Pui CH. Clinical and biological relevance of Immunological marker studies in childhood acute lymphoblastic leukemia. Blood 1993;82(2):343–362.

Pui CH. Acute lymphoblastic leukemia. Pediatr Clin North Am 1997;44(4):831–846.

Pui CH, Christ WM. Biology and treatment of acute lymphoblastic leukemia. J Pediatr 1994;124(4):491–503.

Silverman LB, Weinstein HJ. Treatment of childhood leukemia. Curr Opin Oncol 1997;9(1):26–33.