Transfusion dependence is associated with poor survival in MDS-h and MDS-LB, while transplantation improves outcomes

Abstract Hypoplastic myelodysplastic neoplasms (MDS-h) and MDS with low blasts (MDS-LB) are characterized by low blasts and absence of defining cytogenetic abnormalities, generally conferring better outcomes than other MDS subtypes. We retrospectively analyzed 146 patients with MDS-h and 490 with MDS-LB. Median follow-up was 1168 days and median age was 52 years. MDS-h patients had more severe cytopenias, while MDS-LB showed greater disease burden. U2AF1 (27.29%) and ASXL1 (24.13%) were common mutations. At diagnosis, 42.41% were transfusion-dependent (TD), and 52.08% were Molecular International Prognostic Scoring System (IPSS-M) higher-risk, with comparable rates between subgroups. Among initially transfusion-independent patients (n=368), the cumulative incidence of TD during follow-up was 45.56%, independently predicted by IPSS-M higher-risk (HR=2.065). The estimated 5-year OS was 60.5%, higher in MDS-h (75.6%) than MDS-LB (55.6%, P=0.001). The 5-year cumulative incidence of progression was 14.7%, without subtype difference (P=0.141). TD at diagnosis (HR=3.271), U2AF1 mutations (HR=1.473), age>65 (HR=2.282), and bone marrow blasts≥2% (HR=1.433) were independent adverse predictors for OS. U2AF1 mutations (HR=2.096), bone marrow blasts≥2% (HR=2.105) and IPSS-M higher-risk (HR=2.027) were also associated with progression. In TD patients≤65 years, allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved OS (HR=0.513, P=0.017) and reduced transfusion burden. In this large cohort, we observed a strong association between TD and IPSS-M risk classification. Both MDS-h and MDS-LB patients demonstrated generally favorable survival with low rates of disease progression. Allo-HSCT should be considered for TD patients to improve long-term outcomes.