Interferon alpha for Treatment of Chronic Myeloid Leukemia

Bengt      Simonsson; Henrik      Hjorth-Hansen; Ole      Weis Bjerrum; Kimmo      Porkka

Abstract

Treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-α) was introduced in the early 1980s. Several clinical trials showed a survival advantage for patients treated with IFN-α compared to conventional chemotherapy. Some patients achieved longstanding complete cytogenetic remissions (i.e. > 2 log tumor mass reduction). IFN-α was then recommended as first line medical treatment until 2001. The mechanism of this anti-leukemic effect is not clear, although IFN-α has many effects of potential relevance on stem cells and immunology. There is no evidence of benefit for high dose (in practice a maximally tolerated dose) compared with lower dose IFN-α. When IFN-α is combined with other drugs, we advice lower dose IFN to minimize toxicity and increase treatment adherence and duration. IFN-α combined with Ara-C moderately improves treatment outcome. Imatinib, a tyrosine kinase inhibitor, is now first line treatment for CML, but two large randomized studies show improved outcome when pegylated IFN-α is added to the treatment with imatinib. One explanation for this might be that IFN-α, contrary to imatinib, stimulates the quiescent stem cells to proliferate and thereby potentially increases sensitivity to imatinib. Although imatinib and other tyrosine kinase inhibitors are very efficient, they are rarely curative. IFN-α could be included in curatively aimed combination treatment protocols and thus still be an important element in CML treatment.

Keywords: Interferon-alpha, chronic myeloid leukemia, imatinib, combination therapy, chronic myeloid leukemia stem cells, BCR, BCR-ABL1, CML cell, fluorescent in situ hybridization, allogeneic stem cell transplantation, allogeneic SCT, poietic stern cells, leukemic effect in CML, psychosis, autoimmune disorders, thyreoiditis