Title: Sepsis-Related Mortality in Adults With Acute Leukaemia: A 25-Year National Perspective on Trends and Disparities

Introduction

Sepsis is a major contributor to mortality among adults with acute leukemia in the United States due to profound immunosuppression and intensive anti-cancer therapy. Despite progress in supportive and critical care over the past decades, sepsis-related death among these patients remained a potential clinical burden. This study evaluates U.S. 25-year national trends in sepsis-related mortality among adults aged ≥25 years with acute leukemia.

Methods

We performed a retrospective analysis using the CDC WONDER underlying-cause-of-death (UCD) and multiple cause-of-death (MCD) data from 1999 to 2024. Age-adjusted mortality rate (AAMR) per 100,000 of adults aged ≥ 25 years was extracted using the ICD-10 codes for acute leukemia (C91.0, C92.0, C92.4, C92.5, C93.0, C94.0, C94.2, 94.4, C95.0) with sepsis (A20.7, A22.7, A26.7, A32.7, A40.0-A41, B37.7), and stratified by age, sex, race/ethnicity, U.S. Census region, and urbanization. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC).

Results

A total of 37,290 deaths were attributed to acute leukemia in association with sepsis from 1999 to 2024. The overall mortality trend showed a significant decline (AAPC:-0.98) with temporal variability. Males had markedly higher mortality than females (AAMR: 0.76 vs 0.47), with a significant decline from 2017 to 2024 (APC: −3.71). All age groups had a declining mortality trend, but the highest mortality burden was among Adults aged 65-74 years (crude rate: 2.36), with a significant decline between 2015 and 2024 (APC: -3.39). Across all racial groups, mortality rates demonstrated a sustained downward trend over the study period, with the most pronounced decline among Non-Hispanic White individuals (AAPC: -1.15). Mortality declined across all regions, most prominently in the Northeast (AAPC: -1.67). Both metropolitan and non-metropolitan areas showed a comparable declining trend across the study span (AAPC: -0.52 vs -0.03).

Conclusion

Sepsis- related mortality in adults with acute leukemia has demonstrated a significant decline from 1999 to 2024, with substantial temporal and demographic variability in the U.S. Mortality remained disproportionately advanced among males, older adults, and certain ethnic and regional populations despite harmonious downward trends. These findings suggest sustained progress, while patient inequalities emphasize the need for targeted surveillance, early interventions, and equitable multidisciplinary care.