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CNS-Directed Therapy for Childhood ALL

    Table 2. CNS-Directed Treatment Regimens for Newly Diagnosed Childhood ALL continued...

    Ongoing trials seek to determine whether radiation can be eliminated from the treatment of all children with ALL without compromising survival or leading to increased rate of toxicities from upfront and salvage therapies.[10,11]

    CNS Therapy for Standard-Risk Patients

    Intrathecal chemotherapy without cranial radiation, given in the context of appropriate systemic chemotherapy, results in CNS relapse rates of less than 5% for children with standard-risk ALL.[10,11,12,13,14,15]

    The use of cranial radiation does not appear to be a necessary component of CNS-directed therapy for these patients.[16,17]

    Evidence (triple intrathecal chemotherapy vs. intrathecal methotrexate):

    1. The CCG-1952 study for National Cancer Institute (NCI) standard-risk patients compared the relative efficacy and toxicity of triple intrathecal chemotherapy (methotrexate, prednisone, and cytarabine) with methotrexate as the sole intrathecal agent in nonirradiated patients.[18]
      1. There was no significant difference in either CNS or non-CNS toxicities.
      2. Triple intrathecal chemotherapy was associated with a lower rate of isolated CNS relapse (3.4% ± 1.0% compared with 5.9% ± 1.2% for intrathecal methotrexate; P = .004).
        • This effect was especially notable in patients with CNS2 status at diagnosis (lymphoblasts seen in CSF cytospin, but with <5 WBC/high-power field [hpf] on CSF cell count); the isolated CNS relapse rate was 7.7% ± 5.3% for CNS2 patients who received triple intrathecal chemotherapy compared with 23.0% ± 9.5% for those who received intrathecal methotrexate alone (P = .04).
        • There were more bone marrow relapses in the group that received the triple intrathecal chemotherapy, leading to a worse overall survival (OS) (90.3% ± 1.5%) compared with the intrathecal methotrexate group (94.4% ± 1.1%; P = .01).
        • When the analysis was restricted to patients with precursor B-cell ALL and rapid early response (M1 marrow on day 14), there was no difference between triple and single intrathecal chemotherapy in terms of rates of CNS relapse rate, OS, or event-free survival (EFS).
      3. In a follow-up study of neurocognitive functioning in the two groups, there were no clinically significant differences.[19][Level of evidence: 1iiC]

    CNS Therapy for High-Risk Patients

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