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    Chronic Myelogenous Leukemia Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Chronic-Phase Chronic Myelogenous Leukemia (CML)

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    Among the many unanswered questions are the following:

    • Will responses on tyrosine kinase inhibitors be durable beyond 10 years, and can we ever stop treatment with them? In a prospective, nonrandomized study, 100 patients in complete molecular remission stopped imatinib after more than 2 years of therapy; by 1 year, 61% of patients relapsed and all responded to the reintroduction of imatinib.[24] Longer follow-up is required to see if some patients maintain a long-term remission after discontinuation of therapy.
    • Should the newer tyrosine kinase inhibitors dasatinib or nilotinib replace imatinib as frontline therapy?
    • Does time-to-response matter if a good response is obtained eventually?
    • Does a good response in a high-risk patient overcome the adverse prognosis of the high-risk features?
    • What is the role of allogeneic BMT or SCT for younger, eligible patients and when should it be offered?[14,25,26]
    • Should other active agents be added to therapy with tyrosine kinase inhibitors?[27]

    All of these issues have led to an active reappraisal of recommendations for optimal frontline therapy for chronic-phase CML.

    High-dose therapy followed by allogeneic BMT or SCT

    The only consistently successful curative treatment of CML has been high-dose therapy followed by allogeneic BMT or SCT.[28] Patients younger than 60 years with an identical twin or with HLA-identical siblings can be considered for BMT early in the chronic phase. Although the procedure is associated with considerable acute morbidity and mortality, 50% to 70% of patients transplanted in the chronic phase survive 2 to 3 years, and the results are better in younger patients, especially those younger than 20 years. The results of patients transplanted in the accelerated and blastic phases of the disease are progressively worse.[29,30] Most transplant series suggest improved survival when the procedure is performed within 1 year of diagnosis.[31,32,33][Level of evidence: 3iiiA] The data supporting early transplant, however, have never been confirmed in controlled trials. In a randomized, clinical trial, disease-free survival and OS were comparable when allogeneic transplantation followed preparative therapy with cyclophosphamide and total-body irradiation (TBI) or busulfan and cyclophosphamide without TBI. The latter regimen was associated with less graft-versus-host disease and fewer fevers, hospitalizations, and hospital days.[34][Level of evidence: 1iiA] Reduced-intensity conditioning allogeneic SCT is under evaluation in first or second remissions.[35,36]

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