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Treatment of Recurrent Childhood ALL


    A number of case series describing SCT in the treatment of isolated CNS relapse have been published.[85,86]

    Evidence (SCT):

    1. In a study comparing outcome of patients treated with either HLA-matched sibling transplants or chemoradiotherapy as in the POG studies above, 8-year probabilities of leukemia-free survival adjusted for age and duration of first remission were similar (58% and 66%, respectively).[87][Level of evidence: 3iiiDii] This retrospective, registry-based study included transplantation of both early (<18 months from diagnosis) and late relapses.
      • Because of the relatively good outcome of patients with isolated CNS relapse more than 18 months from diagnosis treated with chemoradiation therapy alone (>75%), transplantation is generally not recommended for this group.
      • The use of transplantation to treat isolated CNS relapse occurring less than 18 months from diagnosis, especially T-cell CNS relapse, requires further study.
      • The use of post-HSCT intrathecal chemotherapy has been controversial, although the most current data suggest no benefit.[48,88]

    Testicular relapse

    The results of treatment of isolated testicular relapse depend on the timing of the relapse. The 3-year EFS of boys with overt testicular relapse during therapy is approximately 40%; it is approximately 85% for boys with late testicular relapse.[89]

    Standard treatment options for childhood ALL that has recurred in the testes include the following:

    1. Chemotherapy.
    2. Radiation therapy.

    The standard approach for treating isolated testicular relapse in North America is to administer chemotherapy plus radiation therapy.

    In some European clinical trial groups, orchiectomy of the involved testicle is performed instead of radiation. Biopsy of the other testicle is performed at the time of relapse to determine if additional local control (surgical removal or radiation) is to be performed. While there are limited clinical data concerning outcome without the use of radiation therapy or orchiectomy, the use of chemotherapy (e.g., high-dose methotrexate) that may be able to achieve antileukemic levels in the testes is being tested in clinical trials.

    Evidence (chemotherapy and radiation therapy):

    1. Dutch investigators treated five boys with a late testicular relapse with high-dose methotrexate during induction (12 g/m2) and at regular intervals during the remainder of therapy (6 g/m2) without testicular radiation. All five boys were long-term survivors.[90]
    2. A study that looked at testicular biopsy at the end of frontline therapy failed to demonstrate a survival benefit for patients with early detection of occult disease.[91]
    3. In a small series of boys who had an isolated testicular relapse after a SCT for a prior systemic relapse of ALL, five of seven boys had extended EFS without a second SCT.[76][Level of evidence: 3iA]

    Treatment Options Under Clinical Evaluation for Recurrent Childhood ALL

    Treatment options under clinical evaluation include the following:

    COG trials for ALL in first relapse

    The COG has divided patients with first relapse into three risk categories as outlined in Table 4. Clinical trials in some risk categories are available.


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