Re-emergence of interferon-α in the treatment of chronic myeloid leukemia

Treatment for chronic myeloid leukemia (CML) has evolved from chemotherapy (busulfan, hydroxyurea) to interferon-alpha (IFN alpha), and finally to tyrosine kinase inhibitors such as imatinib. Although imatinib has profoundly improved outcomes for patients with CML, it has limitations. Most significantly, imatinib cannot eradicate CML primitive progenitors, which likely accounts for the high relapse rate when imatinib is discontinued. IFN alpha, unlike imatinib, preferentially targets CML stem cells. Early studies with IFN alpha in CML demonstrated its ability to induce cytogenetic remission. Moreover, a small percentage of patients treated with IFN alpha were able to sustain durable remissions after discontinuing therapy and were probably cured. The mechanisms by which IFN alpha exerts its antitumor activity in CML are not well understood; however, activation of leukemia-specific immunity may have a role. Some clinical studies have demonstrated that the combination of imatinib and IFN alpha is superior to either therapy alone, perhaps because of their different mechanisms of action. Nonetheless, the side effects of IFN alpha often impede its administration, especially in combination therapy. Here, we review the role of IFN alpha in CML treatment and the recent developments that have renewed interest in this once standard therapy for patients with CML. Leukemia (2013) 27, 803-812; doi:10.1038/leu.2012.313