Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of mutational status.

Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients with therapy-related myelodysplastic syndrome (n=67) who underwent allogeneic transplantation, comparing these patients to similarly treated patients with disease (n=199). The 5-year overall survival was not different between patients with therapy-related and disease (49.9% 53.9%; =0.61) despite a higher proportion of individuals with an Intermediate-2/High International Prognostic Scoring System classification (59.7% 43.7%; =0.003) and high-risk karyotypes (61.2% 30.7%; P<0.01) among the patients with therapy-related disease. In mutational analysis, alteration was the most common abnormality in patients with therapy-related disease (n=18: 30%). Interestingly, the presence of mutations in or in any other the high-risk genes (, , , : n=29: 48%) did not significantly affect either overall survival or relapse-free survival. Allogeneic stem-cell transplantation is, therefore, a curative treatment for patients with therapy-related myelodysplastic syndrome, conferring a similar long-term survival to that of patients with disease despite higher-risk features. While alteration was the most common mutation in therapy-related myelodysplastic syndrome, the finding was not detrimental in our case-series.