In Vitro Activity of Alpha-Interferon on Granulocyte-Macrophage Precursors in Chronic Myeloid Leukemia (CML): Correlation with Clinical Responsiveness
Abstract
Treatment with alpha-interferon (α-IFN) induces an hematologic remission in the majority of early benign phase chronic myeloid leukemia (CML) patients, and cytogenetic improvement is achieved in more than 50% of responding patients. However 20–30% of patients show primary resistance to α-IFN at diagnosis or develop a secondary resistance during α-IFN treatment. The mechanisms through which α-IFN mediates its clinical effects in CML and the reasons for the variable degree of response are still unknown. The results of our study show that the evaluation of the in vitro inhibitory effect of α-IFN on peripheral blood granulocyte-macrophage precursors (PB CFU-GM) before initiating treatment is not a useful predictive parameter of clinical response to α-IFN. Furthermore the lack of cytogenetic conversion in hematologically-responding CML patients does not appear to be due to the selection of a Ph1+ clone more resistant to α-IFN. The data presented here support the hypothesis that the effect of α-IFN in CML is mediated through mechanisms other than direct cytotoxicity against Ph1+ cells.