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Advanced-phase chronic myeloid leukemia.

Author(s): Cortes J, Kantarjian H

Affiliation(s): Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Publication date & source: 2003-01, Semin Hematol., 40(1):79-86.

Publication type: Review

Chronic myeloid leukemia (CML) typically runs a biphasic or triphasic course, with diagnoses usually made in the chronic phase (CP). Without effective treatment, patients eventually progress to a blastic phase (BP), frequently through an intermediate or accelerated phase (AP). Because the definition of AP varies among studies, comparisons of outcome and prognosis are difficult. The management of patients in these advanced phases of the disease has been much less satisfactory than that of patients in CP. Treatment with interferon-alfa (IFNalpha)-based therapy is ineffective for most patients in AP and for all of those in BP. Imatinib mesylate has demonstrated significant activity AP and BP disease, although the results are inferior compared to treatment in CP. In AP, 82% of patients achieve a hematologic response, with 24% achieving a major cytogenetic remission (MCR). Early MCR (within 3 months of diagnosis) provides a survival advantage over patients who do not achieve this response or achieve it later. In BP, 21% of previously treated patients and 36% of previously untreated patients have responded to imatinib, and up to 17% of patients may achieve a major cytogenetic response. However, responses are frequently short-lived. Several agents are being investigated for treatment of advanced-phase CML, including decitabine (DAC), homoharringtonine (HHT), troxacitabine, clofarabine, farnesyl transferase (FTase) inhibitors (FTI), and others. Many have also proven to be synergistic with imatinib in vitro and combination studies are ongoing. Continued investigation of these approaches is needed to improve the long-term prognosis of advanced-phase CML. Copyright 2003, Elsevier Science (USA). All rights reserved.

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