title: A randomized trial comparing interferon-alpha with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase.
abstract: 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. From October 1988 to October 1991, 170 patients were randomized to receive either IFN-alpha or busulfan. Of 159 eligible patients, 31 (38.8%) of 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 partial hematologic remission. A complete cytogenetic response was induced in 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 major (complete and partial) cytogenetic response between the two groups was significant (P = .046). At a median follow-up of 50 months, the predicted 5-year survival rate was 54% in the IFN-alpha group and 32% in the busulfan group (P = .0290), and the predicted 5-year rate of remaining in chronic phase was 41% in the IFN-alpha group and 29% in the busulfan group (P = .1165). As compared with the patients with no cytogenetic response, the patients with any cytogenetic response (complete, partial or minor) after the IFN-alpha or busulfan treatment were significantly 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 significant difference in survival rate in the IFN-alpha group (P = .1065). There was no significant difference in survival rate (P = .3923) and the 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 rate as compared with the busulfan treatment, and unexpectedly, that busulfan can also eliminate Philadelphia chromosome positive clone in a few patients who showed prolonged survival rate and duration of chronic phase.
authors.affiliation: Department of Medicine III, Hamamatsu University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ohnishi
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Tomonaga
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: K
authors.initials: K
authors.lastname: Onozawa
authors.forename: A
authors.initials: A
authors.lastname: Kuramoto
authors.forename: H
authors.initials: H
authors.lastname: Dohy
authors.forename: H
authors.initials: H
authors.lastname: Mizoguchi
authors.forename: S
authors.initials: S
authors.lastname: Miyawaki
authors.forename: K
authors.initials: K
authors.lastname: Tsubaki
mesh_terms: D000328:Adult; D001772:Blood Cell Count; D001853:Bone Marrow / Q000473:pathology; D002066:Busulfan / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D016898:Interferon-alpha; D002066:Busulfan