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Postinduction Treatment for Childhood ALL

    continued...

    Very high-risk ALL

    Approximately 10% to 20% of patients with ALL are classified as very high risk, including the following:[17,26]

    • Infants.
    • Patients with adverse cytogenetic abnormalities, e.g., t(9;22) or t(4;11).
    • Patients with hypodiploidy (<44 chromosomes) and poor response to initial therapy (e.g., high end-induction minimal residual disease [MRD]).
    • Patients with high absolute blast count after a 7-day steroid prophase.
    • Patients who fail induction therapy, even if they achieve complete remission.

    Patients with very high-risk features have been treated with multiple cycles of intensive chemotherapy during the consolidation phase, often including agents not typically used in frontline ALL regimens for standard- and high-risk patients, such as high-dose cytarabine, ifosfamide, and etoposide.[17] However, even with this intensified approach, reported long-term EFS rates range from 30% to 50% for this patient subset.[17,27]

    On some clinical trials, very high-risk patients have also been considered candidates for allogeneic stem cell transplantation (SCT) in first remission, [27,28,29] although it is not clear whether outcomes are better with transplantation.

    Evidence (allogeneic SCT in first remission):

    1. In a European cooperative group study, very high-risk patients (defined as one of the following: morphologically persistent disease after a four-drug induction, t(9;22) or t(4;11), or poor response to prednisone prophase in patients with either T-cell phenotype or presenting white blood cells (WBC) >100,000/μL) were assigned to receive either an allogeneic SCT in first remission (based on the availability of a human lymphocyte antigen–matched related donor) or intensive chemotherapy.[27]
      • Using an intent-to-treat analysis, patients assigned to allogeneic SCT (on the basis of donor availability) had a superior 5-year disease-free survival (DFS) than patients assigned to intensive chemotherapy (57% ± 7% for transplant versus 41% ± 3% for chemotherapy, P = .02)
      • There was no significant difference in overall survival (OS) (56% ± 6% for transplant versus 50% ± 3% for chemotherapy, P = .12).
      • For patients with T- cell ALL and a poor response to prednisone prophase, both DFS and OS rates were significantly better with allogeneic SCT.[28]
    2. In another study of very high-risk patients that included children with extremely high presenting leukocyte counts and children with adverse cytogenetic abnormalities and/or initial induction failure (M2 marrow [between 5% and 25% blasts]), allogeneic SCT in first remission was not associated with either a DFS or OS advantage.[29]
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