High-Risk Myelodysplastic Syndromes: Chemotherapy, Transplantation, and Beyond

Allogeneic hematopoietic cell transplantation (HCT) has curative potential for patients with myelodysplastic syndromes (MDS), though with considerable nonrelapse mortality and morbidity. The International Prognostic Scoring System, despite its confines, remains a widely used tool guiding treatment decisions in MDS. The two hypomethylating agents, 5-azacytidine (azacitidine) and 5-aza-2-deoxycytidine (decitabine), are both effective in high-risk MDS, but about 50% of high-risk MDS patients fail to achieve a meaningful response, and these agents offer only a modest survival benefit, with a median response duration of 13 months. The more recent proposed risk models of MDS, as well as modern transplant strategies and expanded alternative donor sources, have helped to increase the number of patients offered curative treatment. As both drug therapy and HCT modalities evolve, treatment decisions are certain to become more complex. Current therapeutic options should view the hypomethylating agents as a way to optimize disease response before (and possibly after) HCT.