Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue During Interim Maintenance Is Superior To Oral Methotrexate For Children With Standard Risk Acute Lymphoblastic Leukemia (Sr-All): Children'S Oncology Group Study 1991

A substantial number of relapses derive from the NCI standard risk population. CCG-1991 tested two components of the successful COG augmented “BFM” regimen (N Engl J Med 1998; 338:1663) in this subset in a 2 × 2 factorial design. Patients received a 3-drug Induction: vincristine (V), pegylated asparaginase, dexamethasone (D), and intrathecal (IT) cytarabine and methotrexate (M). Patients with an unfavorable early marrow response by morphology (> 25% blasts at day 14, or >25% blasts at day 7 and >5% blasts at day 14) were assigned rescue daunorubicin and “augmented BFM” therapy. Other patients, termed rapid early responders (RER), received Consolidation (daily oral mercaptopurine (MP) and weekly IT M) and were randomized to receive either single or double delayed intensification (DI) phases, and D pulses, oral daily MP, weekly M and monthly V (Reg O) or V and intravenous (IV) escalating dose M with no leukovorin every 10 days for two months preceding and following the DI phase (Reg I).