Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia is a topic covered in the 5-Minute Pediatric Consult.

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Basics

Description

  • Acute lymphoblastic leukemia (ALL) is a hematopoietic malignancy that results from malignant proliferation of immature WBC (B cells and T cells).
  • Risk group classification:
    • Infant ALL: age <1 year
    • Standard risk ALL: age 1 to <10 years; initial WBC count <50,000/μL
    • High-risk ALL: age ≥10 years; WBC ≥50,000/μL
  • Further risk stratification done based on multiple factors including National Cancer Institute (NCI) criteria (age and WBC count), biologic, cytogenetic characteristics, and response to initial therapy. This classification determines the intensity of therapy and prognosis.
    • Low-risk ALL: NCI standard risk group
      • Favorable cytogenetic changes (hyperdiploidy, double trisomies of 4, 10, ETV6/RUNX1 fusion)
      • Pre–B lymphoblasts and negative minimal residual disease (MRD = number of leukemic cells detected by flow cytometry in bone marrow) at end of induction
    • Average-risk ALL: NCI standard risk group
      • Noncontributory cytogenetics
      • Negative MRD at end of induction (<0.01%)
      • No extramedullary (CNS or testicular) involvement, CNS 1
      • Negative MRD at end of induction
    • High-risk ALL: NCI high-risk group
      • Age >10 years regardless of WBC count, extramedullary (CNS 2, 3, or testicular) involvement
      • T-cell phenotype
      • No or very low MRD at end of induction
    • Very high-risk ALL
      • Unfavorable cytogenetics (t[9;22] Philadelphia-positive ALL)
      • Hypodiploidy
      • MLL gene rearrangement, iAMP21
      • Induction failure (>25% lymphoblasts in bone marrow at end of induction)
      • Positive MRD at the end of induction (>0.01%)
    • Other prognostic factors
      • Steroid pretreatment (poor)
      • Down syndrome (poor)
      • Evidence of CNS or testicular disease (poor)

Epidemiology

  • ALL is the most common childhood malignancy.
  • Accounts for approximately 35% of cancer in children
  • More common in Caucasians and males
  • ALL incidence: 3 to 4 cases per 100,000 per year
  • Peak incidence is between ages 2 and 5 years.

Risk Factors

  • Prior cancer therapy (chemotherapy or radiation)
  • Twin with ALL
  • Genetic syndrome listed in the following sections

Genetics

  • Increased risk of leukemia, higher with monozygotic twin
  • Associated genetic syndromes
    • Trisomy 21 (Down syndrome)
    • Fanconi anemia
    • Bloom syndrome
    • Shwachman-Diamond syndrome
    • Ataxia telangiectasia
    • Diamond-Blackfan anemia
  • Neurofibromatosis type 1
  • Li-Fraumeni syndrome (a familial cancer syndrome due to P53 gene mutation)
  • Congenital immunodeficiencies (Wiskott-Aldrich syndrome)

Pathophysiology

  • Leukemia arises from lymphoid progenitor cells that have sustained multiple specific genetic damages that lead to malignant transformation and proliferation, lack of cell maturation, and resistance to normal cell death processes (apoptosis).
  • This lymphoblastic proliferation replaces the normal bone marrow precursor cells, causing ineffective hematopoiesis and infiltration of lymphatic tissue and end organs.

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