ABSTRACT
Based on in vitro data showing that interferon-(IFN-) suppressed stem cell proliferation in both normal and chronic myeloid leukaemia (CML) bone marrow1,2 and on its effect on other tumours, the first clinical studies on the effect of IFN- in CML patients were published in 1983.3
Initially with purified leukocyte IFN- and later with recombinant IFN-, the doses used ranged from 3 to 9 MU/day.4,5
The effect of IFN- was to induce haematologic control of the disease, and in addition suppression of the Philadelphia chromosome (Ph)-positive clone was achieved in a proportion of these patients. Based on these data, and a comparison of complete haematologic response and karyotypic response from other single-agent studies using lower doses of IFN-, over time a standard dose and schedule of IFN- was established of 5 MU/m2 given on a daily basis, with dose reduction permitted in the case of significant toxicity.6-8
A single randomized trial initially addressed the optimal dose of IFN-, and supported the hypothesis that a higher dose given on a daily basis gives a higher rate of haematologic remission.9-11
Over the last decade, a number of large randomized trials comparing IFN- with chemotherapy have been published, with most results showing that the use of IFN- improved survival compared with standard chemotherapy, using either hydroxyurea or busulphan.12-16
Two trials did not show a survival advantage for IFN- over chemotherapy.17,18 However, a meta-analysis of the data has confirmed the survival benefit, with no significant heterogeneity of treatment effect between the trials.19
