title: Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia.
abstract: Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000188:drug therapy*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged
chemical_list: D001215:Asparaginase; D008727:Methotrexate