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Treatment of Recurrent Childhood ALL

    Prognostic Factors in Recurrent Childhood ALL

    The prognosis for a child with acute lymphoblastic leukemia (ALL) whose disease recurs depends on the following factors: [1,2,3,4,5,6,7,8,9,10,11,12,13]; [14][Level of evidence: 3iiDi]

    • Patient characteristics (e.g., age and peripheral blast count at time of relapse).
    • Time from diagnosis to relapse.
    • Site of relapse.
    • Cytogenetics.
    • Immunophenotype.

    Patient characteristics

    Age 10 years and older at diagnosis has been reported as an independent predictor of poor outcome.[13]

    The Berlin-Frankfurt-Münster group has also reported that high peripheral blast counts (>10,000/μL) at the time of relapse were associated with inferior outcomes in patients with late marrow relapses.[10]

    Time from diagnosis to relapse

    For patients with relapsed B-precursor ALL, early relapses fare worse than later relapses, and marrow relapses fare worse than isolated extramedullary relapses. For instance, survival rates after marrow relapse range from less than 20% for patients with marrow relapses occurring within 18 months from diagnosis to 40% to 50% for those whose relapses occur more than 36 months from diagnosis.[5,13]

    For patients with isolated central nervous system (CNS) relapses, the overall survival (OS) rates for early relapse (<18 months from diagnosis) are 40% to 50% and 75% to 80% for those with late relapses (>18 months from diagnosis).[13,15] No evidence exists that early detection of relapse by frequent surveillance (complete blood counts or bone marrow tests) in off-therapy patients improves outcome.[16]

    Site of relapse

    Patients who have combined marrow/extramedullary relapses fare better than those who have isolated marrow relapses.[5,13]

    Patients with marrow relapses who have persistent morphologic disease at the end of the first month of reinduction therapy have an extremely poor prognosis, even if they subsequently achieve a second complete remission (CR2).[17][Level of evidence: 2Di]; [18][Level of evidence: 3iiiA]

    Cytogenetics

    TP53 alterations (mutations and/or copy number alterations) are observed in approximately 11% of patients with ALL at first relapse and have been associated with inferior reinduction failure rate (38.5% TP53 alteration vs. 12.5% TP53 wild-type) and event-free survival (EFS) (9% TP53 alteration vs. 49% TP53 wild-type), of which approximately one-half are newly observed at time of relapse.[19]

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