IFN-alpha Group Research Articles

A Randomized Trial Comparing Interferon-α With Busulfan for Newly Diagnosed Chronic 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. 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.

Inhibitory effects of IFN on N-butyl-N-(hydroxybutyl) nitrosamine induced rats bladder tumors

Bladder tumors were induced in rats by the oral administration of 0.025% N-butyl-N-(hydroxybutyl) nitrosamine (BBN). In order to study the suppressive effects of rat interferon-alpha (IFN-alpha) on induction of carcinogenesis in vivo, rats were treated with IFN-alpha i.m. twice a week. The treatment began at 5th week of BBN administration. The bladder mucosa was observed macroscopically and microscopically, and NK activity was examined. The results were as follows. 1) There was no significant difference in the bladder to body weight ratio between the BBN + IFN-alpha and BBN groups in during stage A (10th-14th week when changes in the mucous membrane such as hypertrophy in the bladder wall or vascular formation are observed). This ratio in the BBN + IFN-alpha group was less than that in the BBN group in during stages B and C (15th-19th week and 20th-30th week respectively when tumors are visually recognizable). 2) The rate of carcinogenesis in the BBN + IFN-alpha group was less than that in the BBN group in stages A and C. 3) The pathological grade and stage of the bladder cancer in the BBN + IFN-alpha group were lower than those in the BBN group in stages B and C. 4) There was no significant difference in NK activity between the two groups in stage A, but NK activity of the BBN + IFN-alpha group was higher than that of the BBN group in stage B. 5) These findings substantiated the hypothesis that IFN-alpha can suppress tumor-growth in BBN induced bladder carcinoma.

Unusual human interferons produced by virus-infected amniotic membranes.

Interferon (IFN) induced in the human amniotic membrane contains at least five different molecular species, as shown by analysis in NaDodSO4/polyacrylamide gels after heating and under reducing conditions. Three of the IFN components reported here--migrating at 26, 43, and 80 kilodaltons--are of unusual antigenic structure because they are neutralized to about the same extent by anti-IFN-alpha and anti-IFN-beta antibodies. The 15- to 17-kilodalton species belongs to the IFN-alpha group, while the 21- to 22-kilodalton species, the most frequently detected major peak, is IFN-beta. In addition to their unusual size and antigenic structure, these IFNs could play a role during embryonic development and in the immune tolerance of the mother with regard to the fetus.