Treatment of Acute Lymphoblastic Leukemia in Children

DISEASE CHARACTERISTICS:

• Diagnosis of acute lymphoblastic leukemia (ALL)

  • No known mature B-cell ALL, defined by the presence of any of the following:

    • Surface immunoglobulin
    • L3 morphology
    • t(8;14)(q24;q32)
    • t(8;22)
    • t(2;8)
  • T-cell surface markers and t(8;14)(q24;q11) allowed

• Meets criteria for 1 of the following risk groups:

  • Standard-risk (SR) disease, defined by the following criteria:

    • 1 to 9 years of age
    • Highest pretreatment WBC < 50,000/mm³

    • No evidence of CNS leukemia, defined by all of the following:

      • Diagnostic lumbar puncture without any cerebrospinal fluid (CSF) blast cells on cytospin (CNS-1) OR < 5 WBC/high-power field (hpf) in CSF with blast cells on cytospin (CNS-2)
      • CNS-1 CSF on days 18 and 32 of study treatment
      • Absence of cranial nerve palsy at diagnosis
    • Absence of T-cell markers on lymphoblasts
    • Absence of t(9;22), mixed-lineage leukemia (MLL) gene translocations, and hypodiploidy < 45 chromosomes by karyotype or fluorescent in situ hybridization (FISH)
    • Minimal residual disease (MRD) level < 0.001 at the end of study remission induction therapy (day 32) OR end-of-induction MRD status cannot be determined

  • High-risk (HR) disease, defined by any of the following criteria:

    • 10 to 17 years of age
    • Highest pretreatment WBC ≥ 50,000/mm³

    • Evidence of CNS leukemia, defined by any of the following:

      • Diagnostic lumbar puncture with ≥ 5 WBC/hpf and blast cells on cytospin (CNS-3)
      • CNS-2 CSF on day 18 or 32 of study treatment
      • CNS-3 CSF on day 18 of study treatment
      • Presence of cranial nerve palsy at diagnosis
    • Predominance of T-cell markers on lymphoblasts

    • Presence of t(9;22)

      • An allogeneic stem cell donor will be sought for transplantation
      • These patients will not receive CNS therapy during study treatment
    • B-lineage and MRD level < 0.001 at the end of study remission induction therapy (day 32) OR end-of-induction MRD status cannot be determined

  • Very high-risk (VHR) disease, defined by any of the following criteria:

    • Presence of MLL gene translocations (i.e., t[4;11]) by karyotype, FISH, or molecular analysis
    • Presence of hypodiploidy < 45 chromosomes by karyotype or FISH analysis
    • MRD level ≥ 0.001 at the end of study remission induction therapy (day 32)
• No secondary ALL

PATIENT CHARACTERISTICS:

• No known HIV positivity
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior therapy except steroids of ≤ 1 week in duration and/or emergent radiation therapy to the mediastinum

  • Patients treated with steroids within the past 7 days will not receive steroid prophase during study treatment