Intensive intravenous methotrexate and mercaptopurine treatment of higher-risk non-T, non-B acute lymphocytic leukemia: A pediatric oncology group study

B. Camitta, D. Mahoney, B. Leventhal, S. J. Lauer, J. J. Shuster, S. Adair, C. Civin, L. Munoz, P. Steuber, D. Strother, B. A. Kamen

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To determine the potential efficacy and toxicity of intravenous (IV) methotrexate (MTX) and mercaptopurine (MP) as postremission intensification treatment for children with B-lineage acute lymphoblastic leukemia (ALL) at higher risk to relapse. Patients and Methods: Eighty-three patients (age 1 to 20 years) with higher-risk B-lineage ALL were entered onto this protocol. Following standard four-drug remission induction, 80 patients received 12 intensive 2-week cycles of MTX/MP: MTX 200 mg/m2 IV push, then 800 mg/m2 IV 24-hour infusion on day 1; MP 200 mg/m2 IV in 20 minutes, then 800 mg/m2 IV 8-hour infusion day 2; MTX 20 mg/m2 intramuscularly day 8; and MP 50 mg/ m2 by mouth days 8 to 14. Age-based triple intrathecal therapy (MTX, hydrocortisone, and cytarabine) was administered for CNS prophylaxis. Continuation therapy was weekly MTX/MP (as on days 8 to 14) for 2 years. Results: Eighty-one patients (98%) entered remission. There were 28 relapses (marrow, n = 11; marrow and CNS, n = 2; isolated CNS, n = 9; testes, n = 5; ovaries, n = 1). No overt relapse occurred during the intensive phase of therapy. The event-free survival (EFS) rate at 4 years is 57.4% ± 9.1% (SE). Hematologic, mucosal, and infectious toxicities were seen in 12%, 9%, and 5% of intensive MTX/MP courses, but were generally mild. Conclusion: Combined data from this and our previous trial suggest that intensive MTX/MP may produce long-term disease-free survival in 70 to 75% of children with B-lineage ALL. In comparison to other intensive regimens, intensive MTX/MP is easy to administer, effective, and relatively nontoxic. If patients at risk for failure of MTX/MP can be identified prospectively, more aggressive regimens could be restricted to this smaller (25% to 30%) cohort.

Original languageEnglish (US)
Pages (from-to)1383-1389
Number of pages7
JournalJournal of Clinical Oncology
Volume12
Issue number7
StatePublished - Jul 1994
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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