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Re-emergence of interferon-? in the treatment of chronic myeloid leukemia.

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

SUBMITTER: Talpaz M

PROVIDER: S-EPMC3703612 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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

Talpaz M M Hehlmann R R Quintás-Cardama A A Mercer J J Cortes J J

Leukemia 20121107 4

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 stu ...[more]

PMID: 23238589

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Project description:The first treatment of chronic myeloid leukemia (CML) included spleen x-radiation and conventional drugs, mainly Busulfan and Hydroxyurea. This therapy improved the quality of life during the chronic phase of the disease, without preventing nor significantly delaying the progression towards advanced phases. The introduction of allogeneic stem cell transplantation (alloSCT) marked the first important breakthrough in the evolution of CML treatment, because about 50% of the eligible patients were cured. The second breakthrough was the introduction of human recombinant interferon-alfa, able to achieve a complete cytogenetic remission in 15% to 30% of patients, with a significant survival advantage over conventional chemotherapy. At the end of the last century, about 15 years ago, all these treatments were quickly replaced by a class of small molecules targeting the tyrosine kinases (TK), which were able to induce a major molecular remission in most of the patients, without remarkable side effects, and a very prolonged life-span. The first approved TK inhibitor (TKI) was Imatinib Mesylate (Glivec or Gleevec, Novartis). Rapidly, other TKIs were developed tested and commercialized, namely Dasatinib (Sprycel, Bristol-Myers Squibb), Nilotinib (Tasigna, Novartis), Bosutinib (Busulif, Pfizer) and Ponatinib (Iclusig, Ariad). Not all these compounds are available worldwide; some of them are approved only for second line treatment, and the high prices are a problem that can limit their use. A frequent update of treatment recommendations is necessary. The current treatment goals include not only the prevention of the transformation to the advanced phases and the prolongation of survival, but also a length of survival and of a quality of life comparable to that of non-leukemic individuals. In some patient the next ambitious step is to move towards a treatment-free remission. The CML therapy, the role of alloSCT and the promising experimental strategies are reviewed in the context of the new therapeutic goals.

Dataset Information

Re-emergence of interferon-? in the treatment of chronic myeloid leukemia.

Publications

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

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