Comparison of two schedules of intermediate-dose methotrexate and cytarabine consolidation therapy for childhood B-precursor cell acute lymphoblastic leukemia: a Pediatric Oncology Group study

J Clin Oncol. 1994 Sep;12(9):1939-45. doi: 10.1200/JCO.1994.12.9.1939.


Purpose: To compare efficacy and toxicity of two schedules of intermediate-dose methotrexate (IDM) and cytarabine (Ara-C) in remission consolidation of childhood acute lymphoblastic leukemia (ALL).

Patients and methods: In 1986, the Pediatric Oncology Group (POG) began a randomized trial to test two schedules of consolidation chemotherapy in children with newly diagnosed B-precursor cell ALL. MTX and Ara-C were given as overlapping 24-hour infusions. The dose and sequence of MTX and Ara-C administration were based on a preclinical model that had demonstrated synergism between these two agents. Two hundred fifteen patients in complete remission were randomized to front-loading consolidation therapy in which six MTX/Ara-C infusions were administered at 3-week intervals from the 7th through the 19th week of therapy. Two hundred thirteen patients in complete remission were randomized to receive standard consolidation therapy in which the six MTX/Ara-C infusions were given every 12 weeks from the 7th through the 67th week of therapy.

Results: Both regimens produced similar rates of adverse side effects, except for a higher incidence of CNS toxicity in individuals randomized to the front-loading arm (32 of 215 v 12 of 213 patients, P = .002). Leukoencephalopathy occurred in three patients on the front-loading regimen and was permanent in one. By Kaplan-Meier analysis, the probability of continuing in complete remission for 5 years was 79% (SE = 5%) and 85% (SE = 5%) for good-risk patients, and 66% (SE = 6%) and 61% (SE = 7%) for poor-risk patients randomized to front-loading and standard regimens, respectively.

Conclusion: Although differences in complete remission durations were not statistically significant by log-rank analysis (P = .62 for good-risk patients, .89 for poor-risk patients, and .99 overall), the results are comparable to those in previous studies using more toxic agents as components of remission consolidation therapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Central Nervous System Diseases / chemically induced
  • Child
  • Child, Preschool
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Drug Administration Schedule
  • Female
  • Humans
  • Infant
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction
  • Risk Factors
  • United States


  • Cytarabine
  • Methotrexate