Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: a report of POG study 9296

PURPOSE: A previous Pediatric Oncology Group (POG) study showed high incidence of secondary acute myelogenous leukemia (AML) in children treated for T-cell acute lymphoblastic leukemia (T-ALL) or higher-stage lymphoblastic lymphoma. To prevent secondary neoplasms, induce prolonged asparagine depletion, and maintain high event-free survival (EFS) in children with newly diagnosed T-ALL or higher-stage non-Hodgkins lymphoma (NHL), we designed this pilot study to determine feasibility and safety of substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase. PATIENTS AND METHODS: Forty-five patients were entered, 29 with T-ALL and 16 with higher-stage NHL. Forty-two of 45 patients achieved complete remission (CR), and 27 completed the therapy in continuous CR. Treatment consisted of 4-week induction then 6 weeks consolidation and ten 9-week maintenance cycles. Therapy primarily comprised antimetabolites, anthracyclines, alkylating agents, and asparaginase. Expected chemotherapy duration was 100 weeks. RESULTS: Forty-two of 45 patients achieved CR, and 27 completed therapy. The most common toxicities were Grade 3 or 4 myelosuppression after cyclophosphamide/cytarabine and allergic reactions to asparaginase. Two died of sepsis early in maintenance. Five-year EFS was 68.5% (SE 9.1%) for T-ALL and 81.3% (SE 9.8%) for NHL. Five-year EFS was 73.1% (SE 6.8%) for the entire cohort. No patients treated entirely on this study developed secondary neoplasms. One patient taken off study for asparaginase toxicity was treated with multiagent therapy that contained teniposide, and died from secondary myelodysplasia (sMDS)/AML. CONCLUSION: Substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase in a dose-intensive regimen was feasible in children and young adults with newly diagnosed T-ALL or higher-stage NHL. EFS was not compromised and secondary neoplasms were decreased.