COMPARISON OF 2 SCHEDULES OF INTERMEDIATE-DOSE METHOTREXATE AND CYTARABINE CONSOLIDATION THERAPY FOR CHILDHOOD B-PRECURSOR CELL ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY

Purpose: To compare efficacy and toxicity of two schedules of intermed iate- dose methotrexate (IDM) and cytarabine (Ara-C) in remission cons olidation of childhood acute lymphoblastic leukemia (ALL). Patients an d Methods: In 1986, the Pediatric Oncology Group (FOG) began a randomi zed trial to test two schedules of consolidation chemotherapy in child ren with newly diagnosed B-precursor cell ALL. MTX and Ara-C were give n as overlapping 24-hour infusions. The dose and sequence of MTX and A ra-C administration were based on a preclinical model that had demonst rated synergism between these two agents. Two hundred fifteen patients in complete remission were randomized to front-loading consolidation therapy in which six MTX/Ara-C infusions were administered at 3-week i ntervals from the 7th through the 19th week of therapy. Two hundred th irteen patients in complete remission were randomized to receive stand ard consolidation therapy in which the six MTX/Ara-C infusions were gi ven every 12 weeks from the 7th through the 67th week of therapy. Resu lts: Both regimens produced similar rates of adverse side effects, exc ept for a higher incidence of CNS toxicity in individuals randomized t o the front-loading arm (32 of 215 v 12 of 213 patients, P = .002). Le u-\koencephalopathy occurred in three patients on the front-loading re gimen and was permanent in one. By Kaplan-Meier analysis, the probabil ity of continuing in complete remission for 5 years was 79% (SE = 5%) and 85% (SE = 5%) for good-risk patients, and 66% (SE = 6%) and 61%(SE = 7%) for poor-risk patients randomized to front-loading and standard regimens, respectively. Conclusion: Although differences in complete remission durations were not statistically significant by log-rank ana lysis (P = .62 for good-risk patients, .89 for poor-risk patients, and .99 overall), the results are comparable to those in previous studies using more toxic agents as components of remission consolidation ther apy. (C) 1994 by American Society of Clinical Oncology.