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Optimizing Treatment of Chronic Myeloid Leukemia: A Rational Approach

Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Correspondence: Richard M. Stone, M.D., Dana-Farber Cancer Institute, 44 Binney Street, Room D-840, Boston, Massachusetts 02115, USA. Telephone: 617-632-2214; Fax: 617-632-2933; e-mail: rstone{at}partners.org

Imatinib mesylate, a novel, molecularly targeted agent for the treatment of chronic myeloid leukemia (CML), has expanded the management options for this disease and provided a paradigm for the treatment of other cancers. Imatinib is a potent, specific inhibitor of BCR-ABL, the constitutively active protein tyrosine kinase critical to the pathogenesis of CML. A randomized, phase III comparison of imatinib with interferon-alfa plus cytarabine as initial treatment for newly diagnosed chronic-phase CML, which demonstrated significantly higher rates of disease response with less toxicity, better quality of life, and a significantly longer progression-free survival time, provided the most persuasive data supporting a major role for imatinib. Currently, allogeneic stem cell transplantation is the only treatment modality with long-term data demonstrating curative potential in CML. An option for less than half of CML patients and associated with substantial morbidity and mortality, transplantation may still be appropriate initial therapy for certain patients. Busulfan and hydroxyurea have no demonstrable effect on disease natural history. The interferon-plus-cytarabine combination can induce durable cytogenetic remissions and was previously the CML pharmacotherapy standard of care, but it is often poorly tolerated. Imatinib is now indicated as first-line therapy for CML in all phases.

Key Words. Leukemia, myeloid, chronic • Stem cell transplantation • Antineoplastic agents • Imatinib • Interferon-alfa

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