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    Childhood Non-Hodgkin Lymphoma Treatment (PDQ®): Treatment - Health Professional Information [NCI] - High-Stage Childhood Anaplastic Large Cell Lymphoma Treatment

    Children and adolescents with high-stage (stage III or IV) anaplastic large cell lymphoma have a disease-free survival of approximately 60% to 75%.[1,2,3,4,5,6] It is unclear which strategy is best for the treatment of high-stage anaplastic large cell lymphoma. The German Berlin-Frankfurt-Munster (BFM) group used six cycles of intensive pulsed therapy, similar to their B-cell non-Hodgkin lymphoma (NHL) therapy (GER-GPOH-NHL-BFM-90 [NHL-BFM-90]).[2]; [7][Level of evidence: 1iiA] Building on these results, the European Intergroup for Childhood NHL (EICNHL) group conducted the FRE-IGR-ALCL99 study (based on the GER-GPOH-NHL-BFM-90 regimen). First, this randomized study demonstrated that methotrexate 1 g/m2 infused over 24 hours plus intrathecal methotrexate and methotrexate 3 g/m2 infused over 3 hours without intrathecal methotrexate yielded similar outcomes.[8][Level of evidence: 1iiC] However, methotrexate 3 g/m2 over 3 hours had less toxicity than methotrexate 1 g/m2 over 24 hours.[8]; [7][Level of evidence: 1iiDi] Secondly, FRE-IGR-ALCL99 randomly assigned patients to limited vinblastine versus prolonged (1 year) vinblastine exposure. Patients receiving the vinblastine plus chemotherapy regimen had a better event-free survival (EFS) in the first year after therapy (91%) than those not receiving vinblastine (74%); however, after 2 years of follow-up, the EFS was 73% for both groups.[9][Level of evidence: 1iiDi] Of note, the Pediatric Oncology Group (POG) trial (POG-9317) demonstrated no benefit of adding methotrexate and high-dose cytarabine to 52 weeks of the APO (doxorubicin, prednisone, and vincristine) regimen.[3] The Italian Association of Pediatric Hematology/Oncology group has used a leukemia-like regimen for 24 months in LNH-92, with similar results as other regimens.[4] The CCG-5941 study tested an approach similar to LNH-92, with more intensive induction and consolidation with maintenance for 1 year total duration of therapy, with similar outcome, but significant hematologic toxicity was observed.[5][Level of evidence: 2A]

    Central nervous system (CNS) involvement in anaplastic large cell lymphoma is rare at diagnosis. In an international study of systemic childhood anaplastic large cell lymphoma, 12 of 463 (2.6%) patients had CNS involvement, three of whom had isolated CNS disease. With multiagent chemotherapy, including high-dose methotrexate, cytarabine, and intrathecal treatment, the event-free survival and overall survival of the CNS-positive group at 5 years were 50% (95% CI, 25%-75%) and 74% (45%-91%), respectively, with a median follow up of 4.1 years. The role of cranial radiation therapy is difficult to assess.[10]

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