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Treatment Option Overview

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    Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of complete cytogenetic response at 12 months was 77% for dasatinib and 66% for imatinib (P = .007).[8][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in nine patients (3.5%) on imatinib and in five patients (1.9%) on dasatinib (not statistically different).

    Although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm this prolonged survival with these agents. The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.[9]

    The only consistently successful curative treatment of CML beyond 10 years' follow-up has been allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT).[10] Long-term data beyond 10 years of therapy are available, and most long-term survivors show no evidence of the BCR/ABL translocation by any available test (e.g., cytogenetics, RT–PCR, or fluorescent in situ hybridization [FISH]). Many patients, however, are not eligible for this approach because of age, comorbid conditions, or lack of a suitable donor. In addition, substantial morbidity and mortality result from allogeneic BMT or SCT; a 15% to 30% treatment-related mortality can be expected, depending on whether a donor is related and on the presence of mismatched antigens.[10]

    Long-term data are also available for patients treated with interferon alpha.[11,12,13] Approximately 10% to 20% of these patients have a complete cytogenetic response with no evidence of BCR/ABL translocation by any available test, and the majority of these patients are disease free beyond 10 years.[10] Maintenance of therapy with interferon is required, however, and some patients experience side effects that preclude continued treatment.

    Newly diagnosed patients with very high levels of circulating leukocytes (WBC >100,000/mm3) require immediate therapy with imatinib mesylate to avoid cerebrovascular events or death from leukostasis. Leukophoresis and plateletpheresis are sometimes required for an even more emergent reduction of counts.

    References:

    1. Sawyers CL: Chronic myeloid leukemia. N Engl J Med 340 (17): 1330-40, 1999.
    2. Druker BJ, Guilhot F, O'Brien SG, et al.: Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355 (23): 2408-17, 2006.
    3. Bhatia R, Holtz M, Niu N, et al.: Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 101 (12): 4701-7, 2003.
    4. Hughes TP, Kaeda J, Branford S, et al.: Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 349 (15): 1423-32, 2003.
    5. Rosti G, Martinelli G, Bassi S, et al.: Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood 103 (6): 2284-90, 2004.
    6. Kantarjian HM, Talpaz M, O'Brien S, et al.: Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 108 (6): 1835-40, 2006.
    7. Saglio G, Kim DW, Issaragrisil S, et al.: Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 362 (24): 2251-9, 2010.
    8. Kantarjian H, Shah NP, Hochhaus A, et al.: Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 362 (24): 2260-70, 2010.
    9. Wei G, Rafiyath S, Liu D: First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol 3: 47, 2010.
    10. Lee SJ, Anasetti C, Horowitz MM, et al.: Initial therapy for chronic myelogenous leukemia: playing the odds. J Clin Oncol 16 (9): 2897-903, 1998.
    11. Ozer H, George SL, Schiffer CA, et al.: Prolonged subcutaneous administration of recombinant alpha 2b interferon in patients with previously untreated Philadelphia chromosome-positive chronic-phase chronic myelogenous leukemia: effect on remission duration and survival: Cancer and Leukemia Group B study 8583. Blood 82 (10): 2975-84, 1993.
    12. Kantarjian HM, Smith TL, O'Brien S, et al.: Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service. Ann Intern Med 122 (4): 254-61, 1995.
    13. Long-term follow-up of the Italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Blood 92 (5): 1541-8, 1998.

    WebMD Public Information from the National Cancer Institute

    Last Updated: February 25, 2014
    This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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