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Treatment for Myelodysplastic Syndromes

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    Combinations of azacitidine with lenalidomide [29] and vorinostat [30] are currently being compared with single-agent azacitidine in a national randomized phase II trial (S1117 [NCT01522976]).

    AML induction-type chemotherapy

    Induction chemotherapy typically used to treat AML may be used to treat patients with higher-risk MDS with excess blasts.[31] Low-dose cytarabine has benefitted some patients; however, this treatment was associated with a higher infection rate when compared with observation in a randomized trial. No difference in time to progression or OS was observed for patients treated with low-dose cytarabine or supportive care.

    Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

    Allogeneic HSCT is the only potentially curative treatment for MDS. Retrospective data suggest cure rates in selected patients ranging from 30% to 60%; outcomes varied with IPSS score at time of transplant, with inferior survival in patients with higher IPSS scores.[32][Level of evidence: 3iiiDiv] The role of cytoreductive therapy in reducing the blast percentage before HSCT remains uncertain. Outcomes may not be as good for patients with treatment-related MDS (5-year disease-free survival of 8% to 30%).[33]

    Although HSCT represents the only treatment modality with curative potential, the relatively high morbidity and mortality of this approach limits its use. A decision analysis predating approval of azacitidine, in patients with a median age younger than 50 years, suggested optimal survival when transplant was delayed until disease progression for lower-risk patients but implemented at diagnosis for higher-risk patients.[34]

    Allogeneic stem cell transplantation with reduced-intensity conditioning (RIC) has extended transplantation as a possible modality for treatment of older patients.[35] In a retrospective analysis of 1,333 patients aged 50 years or older (median, 56 years) who underwent allogeneic transplants for MDS using HLA-matched sibling and unrelated donors, 62% of the patients received RIC HSCT, and the others received standard-dose HSCT. On multivariate analysis, use of RIC and advanced disease stage at transplantation were associated with increased relapse (hazard ratio [HR] of 1.44 and 1.51, respectively).[35][Level of evidence: 3iiiDiv] The predictors of non-relapse mortality included advanced disease stage (HR, 1.43), use of an unrelated donor, and standard dose HSCT (HR, 1.27). The 4-year OS was similar in both groups (30% after myeloablative conditioning vs. 32% in RIC.[35]

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