Intensification with intermediate-dose intravenous methotrexate is effective therapy for children with lower-risk B-precursor acute lymphoblastic leukemia: A pediatric oncology group study

Purpose: To determine whether early intensification with 12 courses of intr avenous (IV) methotrexate (MTX) and IV mercaptopurine (MP) is superior to 1 2 courses of IV MTX alone for prevention of relapse in children with lower- risk B-lineage acute lymphoblastic leukemia (ALL). Patients and Methods: Six hundred fifty-one eligible patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for rem ission induction therapy. Patients were randomized to receive intensificati on with IV MTX 1,000 mg/m(2) plus IV MP 1,000 mg/m2 (regimen A) or IV MTX 1 ,000 mg/m2 alone (regimen C). Twelve courses were administered at 5-week in tervals. Triple intrathecal therapy was used for CNS prophylaxis. Continuat ion therapy included standard oral MP, weekly MTX, and triple intrathecal t herapy every 12 weeks for 2 years. Results: Six hundred forty-five patients (99.1%) achieved remission. Three hundred twenty-five were assigned to regimen A and 320 to regimen C. The es timated 4-year overall continuous complete remission for patients treated w ith regimen A is 82.1% (SE = 2.4%) and for regimen C is 82.2% (SE = 2.6%; P = .5). No significant difference in overall outcome was shown by sex or ra ce. Serious grade 3/4 neurotoxicity, principally characterized by seizures, was observed in 7.6% of patients treated with either regimen. Conclusion: Intensification with 12 courses of IV MTX is an effective thera py for prevention of relapse in children with B-precursor ALL who are at lo wer risk for relapse but may be associated with an increased risk for neuro toxicity. Prolonged infusions of MP combined with IV MTX did not provide ap parent advantage. (C) 2000 by American Society of Clinical Oncology.