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

Abstract

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.

Failure of Hypomethylating Agent–Based Therapy in Myelodysplastic Syndromes

“…However, it also carries significant treatment-related morbidity and mortality that is especially pronounced in older patients with comorbidities. 48,49 Various approaches have been explored in an effort to safely treat patients with a SCT, including appropriate patient selection as well as reduced intensity approaches. The first consideration should be to appropriately choose the population of patients who would benefit the most from an allogeneic SCT, given its inherent toxicity.…”

Current status of allogeneic HST for chronic myelomonocytic leukemia

“…In all, 18 references were selected for full-text analysis. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Two studies were exempt from the age limit inclusion criterion owing to their relative large size and the detailed analysis that was provided by the authors. Kerbauy et al 28 reported on the transplant outcomes of 43 CMML patients age 1-66 years and, more recently, Eissa et al 41 included this same cohort in an updated study of 85 patients with CMML who underwent HST at the Fred Hutchinson Cancer and Research Center.…”

Emerging immunosuppressive drugs in myelodysplastic syndromes

“…A thorough discussion of high-and low-risk MDS therapies was recently reviewed [13][14][15][16][17]. IST remains an effective strategy that has not been widely adopted.…”