Trends and disparities in myelodysplastic Syndrome–Associated mortality in the u.S. from 1999 to 2020: A population-based study using the CDC wonder database

Abstract Background: Myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic disorders characterized by ineffective hematopoiesis, dysplasia of bone marrow lineages, cytopenias, and risk of progression to acute myeloid leukemia. While therapeutic advancements have emerged over the past two decades, population-level outcomes remain poorly defined, especially across demographic and geographic lines. Understanding long-term mortality trends and disparities is essential to inform both clinical strategies and public health interventions. Methods: We conducted a retrospective analysis using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. Adults aged ≥25 years with MDS listed as an underlying or contributing cause of death (ICD-10 codes D46.0–D46.9) between 1999 and 2020 were included. Crude and age-adjusted mortality rates (AAMRs) per 100,000 population were calculated annually. Temporal trends were evaluated using Joinpoint regression to calculate annual percent changes (APCs) with 95% confidence intervals (CIs). Subgroup analyses were performed by sex, race/ethnicity, age group, U.S. Census region, state, and urban–rural classification based on the National Center for Health Statistics schema. Results: From 1999 to 2020, the age-adjusted mortality rate for MDS increased from 4.45 (95% CI: 4.35–4.55) to a peak of 5.17 (95% CI: 5.07–5.27) in 2010 (APC: +2.50%; p=0.0018), followed by a significant decline to 4.39 (95% CI: 4.39–4.47) by 2020 (APC: –2.22%; p0.0001). Throughout the study period, mortality rates were higher in males (AAMR: 6.89; 95% CI: 6.85–6.93) compared to females (AAMR: 3.29; 95% CI: 3.27–3.31). Non-Hispanic Whites had the highest AAMR (4.97), followed by Non-Hispanic Blacks (2.85), Asians/Pacific Islanders (2.76), and Hispanics (2.75). Geographic differences were pronounced. The Midwest had the highest regional AAMR (5.34), while the South had the lowest (4.42). Among urbanization strata, small metropolitan areas reported the highest AAMR (5.17), whereas large central metropolitan areas had the lowest (4.27). At the state level, South Dakota exhibited the highest AAMR (6.64), while Mississippi had the lowest (2.94), reflecting a more than twofold difference in MDS-related mortality across states. Conclusion: This national population-based analysis spanning over two decades demonstrates evolving mortality patterns in MDS, with a rise in deaths from 1999 to 2010 followed by a significant decline thereafter. The observed decline may reflect improvements in diagnostic capabilities, supportive care, and therapeutic options. However, marked disparities persist across sex, race/ethnicity, region, and urbanization levels. Particularly concerning are the elevated mortality rates in small metropolitan areas and certain states, suggesting persistent inequities in healthcare access, early diagnosis, and treatment availability. These findings underscore the urgent need for targeted, equity-focused interventions to improve MDS outcomes in underserved populations.