Longitudinal trends (1999–2023) and forecasted mortality (2024–2030) in sepsis-associated mortality among patients with Myelodysplastic Syndromes in the United States.

Abstract Background: Myelodysplastic Syndromes (MDS) are clonal hematopoietic neoplasms that lead to dysplasia and ineffective hematopoiesis within the bone marrow. MDS compromises innate and adaptive immunity, placing patients at high risk for severe infections, particularly sepsis. Given the aging U.S. population and increasing MDS diagnoses, understanding sepsis-related mortality trends is crucial. Objective: To analyze national trends in sepsis-related mortality among MDS patients (1999–2023), assess demographic disparities, and forecast mortality through 2030. Methods: We analyzed CDC WONDER “Multiple Cause of Death” data (1999–2023), identifying deaths listing both MDS (ICD-10: D46) and sepsis (A41). Age-adjusted mortality rates (AAMR) were calculated per million persons using the 2000 U.S. standard population. Trends were evaluated via Joinpoint regression to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC) with 95% confidence intervals (CI). ARIMA models with Box-Cox transformation were fitted after ADF/KPSS tests to forecast AAMR through 2030. Results: From 1999 to 2023, 20,187 sepsis-related deaths occurred among individuals with MDS in the U.S. The overall age-adjusted mortality rate (AAMR) declined from 18.2 per million (95% CI: 16.7–19.6) in 1999 to 16.7 per million (95% CI: 15.6–17.8) in 2023. Males had higher mortality than females, with AAMR decreasing from 28.2 to 23.9; a temporary rise occurred between 2015–2016 (29.0 to 31.8), followed by intermittent rebounds. Female AAMR remained stable, ranging from 10.9 to 13.7, ending at 11.5 in 2023. White individuals experienced the highest number of MDS-associated sepsis deaths (n=17,931), with a relatively stable AAMR of 18.4 in 1999 and 17.6 in 2023. Black individuals saw a modest decline in AAMR from 17.7 to 14.3, accounting for 1,528 deaths. Asian or Pacific Islander individuals, with data available from 2004–2020, had 451 deaths and a significant AAMR decrease from 24.2 to 15.5, indicating notable improvement in this group. In 2023, the Northeast had the highest regional AAMR (21.5), followed by the Midwest (18.9), South (15.2), and West (14.7). Small metro areas had the greatest urbanization-related burden (AAMR 19.3), while large central metros reported lower rates (15.7); rural areas remained disproportionately affected (18.5). ARIMA-based projections forecast a continued rise in MDS-associated sepsis mortality through the end of the decade. The projected AAMRs are 18.72 (95% CI: 15.5–21.6) in 2026, 18.87 (95% CI: 15.7–21.8) in 2028, and 19.02 (95% CI: 15.7–21.8) in 2030. This forecast indicates a plateauing but persistent burden, particularly for high-risk subgroups and underserved regions. Conclusion: Sepsis-related mortality in patients with MDS has steadily increased over the past two decades, with projections indicating continued upward trends through 2030. The disproportionate burden on males, Black individuals, and residents in rural and Southern states highlights the need for improved infection prevention strategies, early recognition, and tailored care delivery for high-risk populations.