Curability of Burkitt's lymphoma with high-dose cyclophosphamide-high-dose methotrexate therapy and intrathecal chemoprophylaxis.

Abstract

Twenty-four children with Burkitt's lymphoma were treated beginning May 1976 with a regimen alternating high doses of cyclophosphamide and methotrexate in induction and consolidation; only high doses of methotrexate were used in the maintenance phase. Throughout therapy, which was planned for 54 weeks, intrathecal chemoprophylaxis using methotrexate, cytosine arabinoside, and hydrocortisone was coordinated with the high-dose methotrexate infusion therapy to provide CNS chemoprophylaxis that maintained therapeutic methotrexate spinal fluid levels (greater than 10(-6) mol/L) for approximately 60 hours. Twenty-two (92%) of the 24 children attained complete remission; two (8.3%) patients attained only partial remission, failing therapy. Two children died of infection while in complete remission; two children relapsed on therapy. Actual survival is 75%; the median follow-up time is 38+ months (range, 1 1/2+ to 84+ months). Relapses correlated with Murphy disease stage as follows: stage I--0/3, stage II--2/7, stage III--2/10, and stage IV--0/2. Serious side effects and toxicities of chemotherapy occurred in ten patients (metabolic disturbances after rapid tumor lysis, two; infectious and/or febrile episodes following cyclophosphamide therapy, three; methotrexate side effects, four; and complications of intrathecal therapy, one). Results of this therapy are similar to those of the best regimens that have been reported. Treatment has been adapted for use in Burkitt's lymphoma by the Pediatric Oncology Group; the responsiveness of other B cell lymphomas of childhood to this treatment is also being determined.