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  • Title: Methotrexate and asparaginase combination chemotherapy in refractory acute lymphoblastic leukemia of childhood.
    Author: Lobel JS, O'Brien RT, McIntosh S, Aspnes GT, Capizzi RL.
    Journal: Cancer; 1979 Mar; 43(3):1089-94. PubMed ID: 284840.
    Abstract:
    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.
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