Consolidation therapy with antimetabolite-based therapy in standard-risk acute lymphocytic leukemia of childhood: A pediatric oncology group study

Purpose: To develop antimetabolite-based consolidation regimens that minimize acute and long-term toxicities and improve the survival rate of children with standard-risk B-lineage acute lymphocytic leukemia (ALL). Patients and Methods: Seven hundred twenty-seven eligible patients with standard-risk early pre-B ALL were registered onto the study Seven hundred sixteen patients attained a complete remission (CR) after induction therapy. Of these, 114 patients were randomized to a different regimen and were the subject of a separate report. Six hundred two patients were randomized to receive one the following regimens: intermediate-dose methotrexate (IDMTX) with leucovorin rescue on weeks 7, 10, 13, 14 19, and 22 (regimen A); regimen A plus asparaginase (ASP) administered intramuscularly (IM) weekly for 24 weeks (regimen B); or regimen A plus a 24-hour infusion of cytarabine (AraC) with each IDMTX (regimen C), After consolidation, patients were placed on maintenance therapy through week 156, Regimens A and C were opened in February 1986, and regimen B in May 1987, Comparisons are based on concurrently randomized patients (May 1987 to January 1991 between regimens A and B, and February 1986 to January 1991 between regimens A and C). Results: The 5-year continuous CR (CCR) rated were not significantly different: A versus B, 78.1% (3.9 +/- SE) versus 83.3% +/- 3.5% and A versus C, 79.4% +/- 3.2% versus 83.5% +/- 2.9%; P by one-sided log-rank tests were .27 and .34, respectively, Significant treatment differences were not found with regard to sex, rate of testicular and CNS relapse, or CNS complications. During consolidation, regimen C had significantly more bacterial infections (P =.0032) and days spent in the hospital(P <.001) compared with regimen A. Conclusion: We were unable to show a statistical advantage of adding either ASP or AraC to IDMTX in terms of improvement in event-free survival (EFS), J Clin Oncol 16:2840-2847, (C) 1998 by American Society of Clinical Oncology.