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

Michael B. Harris, Jonathan J. Shuster, D. Jeanette Pullen, Michael J Borowitz, Andrew J. Carroll, Fred G. Behm, Vita J. Land

Research output: Contribution to journalArticle


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, 16, 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) rates 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).

Original languageEnglish (US)
Pages (from-to)2840-2847
Number of pages8
JournalJournal of Clinical Oncology
Issue number8
Publication statusPublished - Aug 1998
Externally publishedYes


ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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