The Memorial Sloan-Kettering-New York-I1 Protocol

Background. Improved survival of children with acute lymphoblastic leukemia (ALL) has made it more difficult to develop new protocols to further improve results. The authors report the pilot experience with the Memorial Sloan-Kettering-New York-11 (MSK-NY -11) protocol, based on the New York regimen with changes made in an attempt to improve efficacy while reducing toxicity. Methods. Forty-four of 46 consecutive patients were randomized to one of four regimens varying only in the sequence and mode of administration of the drugs during the first 48 hours of therapy, while the kinetics of the disappearance of the leukemic cells from the bone marrow was monitored with bone marrow aspirates and biopsies on days 0, 2, 7, and 14. Results. Thirty-two high-risk and 12 average-risk patients were randomized. The marrow contained less than 25'/0 blasts in 74.4% and 92.9% by day 7 and 14, respectively. Ninety-three percent achieved remission. Regimens beginning with daunorubicin achieved a greater and more rapid reduction in leukemic cells than those starting with cyclophosphamide. Daunorubicin infusion produced a more rapid cytoreduction than daunorubicin bolus. Two of 41 patients who achieved remission relapsed, and there was one death in remission. With a median follow-up of 54+ months, the event-free survival (EFS) rate was 86% ? 10%. Disease-free survival (DFS) rate at 48 months was 93%. The estimated 4-year EFS rate for the high-risk and average-risk patients were 83 .+ 14% and 93 ? lo%, respectively. Four of 18 patients given daunorubicin bolus and 0 of 18 patients given daunorubicin infusion who were monitored with serial echocardio-

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