Therapy of refractory adult acute lymphoblastic leukemia with vincristine and prednisone plus tandem methotrexate and L-asparaginase: results of a cancer and leukemia group B study

Methotrexate (MTX) and L-asparaginase (ASP) are effective agents in the treatment of acute lymphoblastic leukemia (ALL). The effects of combining MTX and ASP are schedule dependent. To investigate this schedule dependency, the Cancer and Leukemia Group B (CALGB) employed vincristine and prednisone with progressive dose escalation of moderate-dose MTX (125 mg/m2) followed 24 h later with ASP (6,000 U/m2) in refractory adult ALL. We treated 38 patients with refractory or first relapse adult ALL. Most patients had received prior ASP (92%) and MTX (72%). A complete remission was achieved in 25% with a median duration of remission of 21 weeks. The median survival for the entire group was 7.4 months. Therapy was well tolerated and toxicity was acceptable. Our response rate was lower than other tandem MTX and ASP adult ALL trials. Therapy was similar with other series, with the exception of the dose of ASP employed. We conclude that tandem MTX and ASP, in the doses and schedule used here, has only modest activity in previously treated adult ALL. This regimen offers little advantage to other salvage regimens.