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Treatment of Recurrent Childhood ALL

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    With improved success in treating children with ALL, the incidence of isolated extramedullary relapse has decreased. The incidence of isolated CNS relapse is less than 5%, and testicular relapse is less than 1% to 2%.[77,78,79] Age older than 6 years at diagnosis is an adverse prognostic factor for patients with an isolated extramedullary relapse.[80] In the majority of children with isolated extramedullary relapses, submicroscopic marrow disease can be demonstrated using sensitive molecular techniques,[81] and successful treatment strategies must effectively control both local and systemic disease. Patients with an isolated CNS relapse who show greater than 0.01% MRD in a morphologically normal marrow have a worse prognosis than patients with either no MRD or MRD less than 0.01%.[81]

    CNS relapse

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

    1. Systemic and intrathecal chemotherapy.
    2. Cranial or craniospinal radiation.

    While the prognosis for children with isolated CNS relapse had been quite poor in the past, aggressive systemic and intrathecal therapy followed by cranial or craniospinal radiation has improved the outlook, particularly for patients who did not receive cranial radiation during their first remission.[15,82,83,84]

    Evidence (chemotherapy and radiation therapy):

    1. In a Pediatric Oncology Group (POG) study using this strategy, children who had not previously received radiation therapy and whose initial remission was 18 months or longer had a 4-year EFS rate of approximately 80% compared with EFS rates of approximately 45% for children with CNS relapse within 18 months of diagnosis.[84]
    2. In a follow-up POG study, children who had not previously received radiation therapy and who had initial remission of 18 months or more were treated with intensive systemic and intrathecal chemotherapy for 1 year followed by 18 Gy of cranial radiation only.[15] The 4-year EFS was 78%. Children with an initial remission of less than 18 months also received the same chemotherapy but had craniospinal radiation (24 Gy cranial/15 Gy spinal) as in the first POG study and achieved a 4-year EFS of 52%.
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