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

M Talpaz1, R Hehlmann2, A Quintás-Cardama3, J Mercer1 and J Cortes3

1Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
2III Medizinische Universitätsklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Mannheim, Germany
3Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence: Dr M Talpaz, Department of Internal Medicine, Division of Hematology Oncology, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, CCC Room 4302, Ann Arbor, MI 48109-5936, USA. E-mail: mtalpaz@med.umich.edu

Received 2 March 2012; Revised 2 October 2012; Accepted 8 October 2012
Advance online publication 14 December 2012

Abstract
Treatment for chronic myeloid leukemia (CML) has evolved from chemotherapy (busulfan, hydroxyurea) to interferon-α (IFNα), 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. IFNα, unlike imatinib, preferentially targets CML stem cells. Early studies with IFNα in CML demonstrated its ability to induce cytogenetic remission. Moreover, a small percentage of patients treated with IFNα were able to sustain durable remissions after discontinuing therapy and were probably cured. The mechanisms by which IFNα 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 IFNα is superior to either therapy alone, perhaps because of their different mechanisms of action. Nonetheless, the side effects of IFNα often impede its administration, especially in combination therapy. Here, we review the role of IFNα in CML treatment and the recent developments that have renewed interest in this once standard therapy for patients with CML.

read full article here:    http://www.nature.com/leu/journal/v27/n4/full/leu2012313a.html