Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leukemia of childhood.
Two groups of children with refractory acute lymphoblastic leukemia were treated with a regimen of methotrexate (MTX) and asparaginase (Asn'ase) based on studies of the effect of MTX in vitro on human lymphoblasts exposed to Asn'ase. Induction therapy in 12 children produced 4 complete remissions, 3 partial remissions, and 5 failures. Responsiveness to Asn'ase seemed necessary for successful induction with the drug combinations. Maintenance therapy in 18 children produced a median hematologic remission of 31 weeks (range 3-85 weeks). During remission, 2 children developed central nervous system leukemia and 2 died of infection. The mean maximally tolerated dose of MTX was 361 mg/m2. The results of this trial suggest therapeutic synergy in maintenance therapy and the capability of Asn'ase to attenuate MTX toxicity.
D000293:Adolescent; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D001853:Bone Marrow / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D008297:Male; D008577:Meningeal Neoplasms; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009362:Neoplasm Metastasis; D012075:Remission, Spontaneous
D001215:Asparaginase; D008727:Methotrexate