IMPROVED OUTCOME WITH DELAYED INTENSIFICATION FOR CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA AND INTERMEDIATE PRESENTING FEATURES - A CHILDRENS-CANCER-GROUP PHASE-III TRIAL

Purpose: The Berlin-Frankfurt-Munster (BFM) 76/79 trial of acute lymphoblastic leukemia (ALL) in children produced impressive disease-free survival (DFS) rates with a protocol that began with 8 weeks of intensive therapy, followed by 8 weeks of maintenance therapy, and then another 6 weeks of intensive treatment. The current study was conducted to determine the relative contributions of each of these periods of intense therapy on the DFS rates of ALL patients with intermediate presenting features. In addition, due to concerns regarding the toxicity of CNS irradiation, we compared cranial irradiation (CXRT) with intrathecal methotrexate (IT MTX) administered during induction and consolidation to IT MTX during all phases of the treatment program. Patients and Methods: Between May 1983 and April 1989, more than 1,600 children with ALL and intermediate presenting features, as defined by the Childrens Cancer Group (CCG), were entered into a randomized trial that tested four systemic therapy regimens and two CNS programs. Results: The results with a median follow-up of 57 months show that systemic regimens with a delayed intensification (Dellnt) phase of therapy had a 5-year event-free survival (EFS) rate of 73% compared with the control regimen EFS rate of 61 % (P = .006). For children less than 10 years of age, standard three-drug induction and Dellnt produced a 77% 5-year EFS. IT MTX during all phases of therapy provided CNS protection comparable to the CXRT regimen in children less than 10 years of age. Children 10 years of age or older appear to have a better EFS rate with intensive induction, Dellnt, and CXRT. Conclusion: Dellnt improves the EFS rate of children with ALL and intermediate presenting features. Maintenance IT MTX can be safely substituted for CXRT for presymptomatic CNS therapy in children with intermediaterisk characteristics less than 10 years of age. © 1993 by American Society of Clinical Oncology.