A RANDOMIZED TRIAL COMPARING INTERFERON-ALPHA WITH BUSULFAN FOR NEWLY-DIAGNOSED CHROMIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE

A multicenter randomized study was conducted to compare the effect of interferon-alpha (IFN-alpha) with that of busulfan in newly diagnosed patients with chronic myelogenous leukemia (CML) in chronic phase. Fro m October 1988 to October 1991, 170 patients were randomized to receiv e either IFN-alpha or busulfan. Of 159 eligible patients, 31 (38.8%) o f 80 patients in the IFN-alpha group and 43 (54.4%) of 79 patients in the busulfan group achieved complete hematologic remission, and 38.8% in the IFN-alpha group and 43.0% in the busulfan group achieved partia l hematologic remission. A complete cytogenetic response was induced i n seven (8.8%) of 80 patients treated with IFN-alpha and two (2.5%) of 79 patients treated with busulfan, and a partial cytogenetic response was 7.5% (6/80) and 2.5% (2/79), respectively. The difference in majo r (complete and partial) cytogenetic response between the two groups w as significant (P = .046). At a median followup of 50 months, the pred icted 5-year survival rate was 54% in the IFN-alpha group and 32% in t he busulfan group (P = .0290), and the predicted 5-year rate of remain ing in chronic phase was 41% in the IFN-alpha group and 29% in the bus ulfan group (P = .1165). As compared with the patients with no cytogen etic response, the patients with any cytogenetic response (complete, p artial or minor) after the IFN-alpha or busulfan treatment were signif icantly superior in the duration of chronic phase (IFN-alpha group; P = .0017, busulfan group; P = .0010) even after correction for the time to response using the landmark analysis. However, there was no signif icant difference in survival rate in the IFN-alpha group (P = .1065). There was no significant difference in survival rate (P = .3923) and t he duration of chronic phase (P = .6258) between the IFN-alpha and the busulfan group in the patients with a cytogenetic response (complete, partial or minor). These results demonstrate that IFN-alpha treatment produces a significantly superior cytogenetic response and survival r ate as compared with the busulfan treatment, and unexpectedly, that bu sulfan can also eliminate Philadelphia chromosome positive clone in a few patients who showed prolonged survival rate and duration of chroni c phase. (C) 1995 by The American Society of Hematology.