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Treatment of Recurrent Childhood ALL

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    Immunophenotype

    Immunophenotype is an important prognostic factor at relapse. Patients with T-cell ALL who experience a marrow relapse (isolated or combined) at any time during treatment or posttreatment have a very poor prognosis.[5]

    Other factors

    Other prognostic factors for recurrent ALL include the following:

    1. The Children's Oncology Group (COG) reported that risk group classification at the time of initial diagnosis was prognostically significant after relapse; patients who met National Cancer Institute (NCI) standard-risk criteria at initial diagnosis fared better after relapse than did NCI high-risk patients.[13]
    2. Several studies have demonstrated that minimal residual disease (MRD) levels after the achievement of CR2 are of prognostic significance in relapsed ALL.[17,20,21,22]; [23][Level of evidence: 3iiiDi] High levels of MRD at the end of reinduction and at later time points have been correlated with an extremely high risk of subsequent relapse.

    Standard Treatment Options for Recurrent Childhood ALL

    Treatment of bone marrow relapse

    Standard treatment options for reinduction therapy when cancer has recurred in the bone marrow include the following:

    1. Chemotherapy.

    Standard treatment options for postreinduction therapy when cancer has recurred in the bone marrow include the following:

    1. Chemotherapy (for B-precursor ALL).
    2. Stem cell transplantation.

    Reinduction chemotherapy

    Initial treatment of relapse consists of induction therapy to achieve a CR2. Using either a four-drug reinduction regimen (similar to that administered to newly diagnosed high-risk patients) or an alternative regimen including high-dose methotrexate and high-dose cytarabine, approximately 85% of patients with a marrow relapse achieve a CR2 at the end of the first month of treatment.[5]; [24][Level of evidence: 2A]; [17][Level of evidence: 2Di] Patients with early marrow relapses have a lower rate of achieving a morphologic CR2 (approximately 70%) than do those with late marrow relapses (approximately 95%).[17,24]

    Evidence (mitoxantrone):

    1. A United Kingdom-based randomized trial of patients with relapsed ALL compared reinduction with a four-drug combination using idarubicin versus mitoxantrone. [25][Level of evidence: 1iiA]
      • A significant improvement in OS in the mitoxantrone arm (69% vs. 45%, P = .007) due to decreased relapse was reported.

      The potential benefit of mitoxantrone in relapsed ALL regimens requires further investigation.

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