REPETITIVE LOW-DOSE ORAL METHOTREXATE AND INTRAVENOUS MERCAPTOPURINE TREATMENT FOR PATIENTS WITH LOWER RISK B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP PILOT-STUDY

Background. This trial evaluated the toxicity and preliminary efficacy of a repeated oral low dose (LD) methotrexate schedule with intraveno us mercaptopurine infusions as intensification therapy for children wi th lower risk B-lineage acute lymphoblastic leukemia (ALL). Patients a nd Methods. From December 1986 to January 1991, 96 children with newly diagnosed, lower risk ALL were enrolled. Vincristine, L-asparaginase, and prednisone were used for remission induction. Age-based methotrex ate was administered intrathecally (IT) for central nervous system (CN S) prophylaxis. An outpatient-based intensification treatment included LD methotrexate 30 mg/M(2) every 6 hours for 5 doses, followed by int ravenous mercaptopurine 1000 mg/M(2) for 6 hours every 2 weeks for 12 courses. Leucovorin rescue was administered 48 hours after methotrexat e treatment was begun. Maintenance therapy included standard daily ora l mercaptopurine, weekly intramuscular methotrexate, and IT methotrexa te every 12 weeks, for 2 years. Results. All patients had disease remi ssion. Thirty-two patients relapsed; there were 17 isolated bone marro w relapses, 10 isolated CNS relapses, 2 isolated testicular relapses, 1 marrow plus CNS relapse, 1 marrow plus testicular relapse, and 1 CNS plus testicular relapse. Event free survival (EFS) at 4 years was 66% (standard error, 7%) by Kaplan-Meier analysis. Complications associat ed with LD methotrexate/mercaptopurine courses were few and resulted i n hospital readmissions in 2.4% of courses. Two patients were unable t o comply with the oral LD methotrexate schedule and received intraveno us methotrexate. Three patients were unable to complete scheduled main tenance because of hepatic or hematopoietic dysfunction. Conclusions. Low dose methotrexate/mercaptopurine can be administered safely on an outpatient basis to children with lower risk B-lineage ALL. However, t here was a higher than expected incidence of bone marrow and CNS relap se. The reasons for this outcome were not completely clear but raise t he possibility that LD methotrexate therapy may be less effective in p reventing relapse than are higher dose, parenteral methotrexate regime ns.