EXTENDED INTRATHECAL METHOTREXATE MAY REPLACE CRANIAL IRRADIATION FORPREVENTION OF CNS RELAPSE IN CHILDREN WITH INTERMEDIATE-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA TREATED WITH BERLIN-FRANKFURT-MUNSTER-BASED INTENSIVE CHEMOTHERAPY

Purpose: To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiatio n in intermediate-risk acute lymphoblastic leukemia (ALL) children tre ated with a Berlin-Frankfurt-Munster (BFM)-based intensive chemotherap y. Patients: Three hundred ninety-six children with non-B-ALL were enr olled onto the Associazione Italiana di Ematologia ed Oncologic Pediat rica (AIEOP) ALL 88 study. Standard risk (88) included patients with l ow tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) w ere patients with an RI greater than or equal to 0.8 but less than 1.2 ; and high risk (HR) were those with an RI greater than or equal to 1. 2 or CNS involvement at diagnosis. The treatment schedule was a modifi ed version of the ALL-BFM 86 study. CNS-directed treatment consisted o f high-dose methotrexate (HD-MTX; 5 g/m(2) for four courses) plus intr athecal methotrexate (IT-MTX; nine doses); IR patients additionally re ceived extended IT-MTX (nine doses during continuation therapy); crani al irradiation was given only to HR patients. Results: Of the 375 (94. 7%) children who achieved remission, 1.3% had an adverse event other t han relapse, The estimated event-free survival (EFS) at 6 years was 66 .6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in t he IR patients, and 54.5% (3.7) in the HR patients, Relapse occurred i n 107 children (27.0%). Isolated CNS relapse occurred in 20 children ( 5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1 %) in the HR group. The estimated 6-year CNS leukemia-free survival wa s 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group, Conclusion: Cranial irradi ation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given . Because the CNS disease control was less complete in the SR group, t hese data challenge the effectiveness of HD-MTX for protection from CN S disease and support the protective role of extended intrathecal chem otherapy. (C) 1995 by American Society of Clinical Oncology.