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Chronic-Phase Chronic Myelogenous Leukemia

    continued...

    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.[26] 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.[27,28] Most transplant series suggest improved survival when the procedure is performed within 1 year of diagnosis.[29,30,31][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.[32][Level of evidence: 1iiA] Reduced-intensity conditioning allogeneic SCT is under evaluation in first or second remissions.[33,34]

    About 20% of otherwise eligible CML patients lack a suitably matched sibling donor.[35] HLA-matched unrelated donors or donors mismatched at one-HLA antigen can be found for about 50% of eligible participants through the National Marrow Donor Program.[35] A retrospective review of 2,444 patients who received myeloablative allogeneic SCT showed OS at 15 years of 88% (95% confidence interval [CI], 86%–90%) for sibling-matched transplant and of 87% (95% CI, 83%–90%) for unrelated donor transplant.[36] The cumulative incidences of relapse were 8% (95% CI, 7%–10%) for sibling-matched transplant and 2% (95% CI, 1%– 4%) for unrelated donor transplant.[36]

    Although the majority of relapses occur within 5 years of transplantation, relapses have occurred for as long as 15 years following BMT.[37] In a molecular analysis of 243 patients who underwent allogeneic BMT over a 20-year interval, only 15% had no detectable BCR/ABL transcript by PCR analysis.[38] The risk of relapse appears to be less in patients transplanted early in disease and in patients who develop chronic graft-versus-host disease.[28,39]

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