Background: Sepsis is a frequent and life-threatening complication in acute myeloid leukemia (AML), driven by disease-related immune dysfunction and chemotherapy-induced immunosuppression. However, population-level data on long-term trends in sepsis-related mortality among AML patients are limited. We aimed to characterize national patterns in sepsis-related mortality over the past 24 years, with emphasis on demographic and geographic variations to help identify care gaps and healthcare disparities.

Methods: We performed a retrospective, population-based study using CDC WONDER mortality data from 1999–2023. AML decedents with sepsis listed as an underlying or contributing cause of death were identified using ICD-10 codes C92.0, A40–A41, B37.7 and B44.7. We described demographics for age in ten-year intervals, sex, census region, urbanization, and place of death. We analyzed population level data using Age-adjusted mortality rates (AAMRs), and trends were analyzed based on annual percentage change (APC) using Joinpoint regression. Statistical significance was noted for p<0.05 and 95% CIs were reported.

Results: A total of 27,328 sepsis-related deaths among AML patients were identified. Of these, age group 65-74 had the highest proportion of deaths (30.8%), followed by 55-64 (22.8%) and 75-84 (21.8%). 41.6% of deaths were in females. By region, South had the highest proportion of deaths (37.4%), followed by West (21.9%), Midwest (21.7%) and Northeast (19.9%). Per urbanization, 53.7% of death were in large metro area, followed by 30.9% in medium/small metro and 12.4% in non-metro. Lastly, majority of sepsis related deaths were noted to be in inpatient medical facility (90.0%), followed by home (4.5%), hospice/nursing facility (3.8%) and then outpatient/emergency room (1.4%).

On analyzing the trends, mortality rates rose significantly in patients aged 65–74 (APC 0.61, 95% CI 0.10–6.46, p=0.032) and 75–84 years (APC 2.98, 95% CI 2.62–4.16, p<0.001) until 2018–2019, followed by significant declines (APC –2.94, 95% CI –11.43 to –0.06, p=0.043). Similar downward trends from 2016 onward were observed in younger cohorts age groups 45–54 (APC –3.89, p<0.001) and 55–64 (APC –3.27, p<0.001). Geographic patterns also varied. AAMRs declined in the Northeast (APC –0.49, p=0.030), but increased in the West until 2016 (APC 1.81, p=0.002).

Conclusions: Sepsis-related mortality remains a major contributor to deaths among AML patients. Mortality increased until 2018–2019 in older age groups, followed by declines in most age groups, potentially reflecting improvement in supportive care and wider adoption of less intensive therapies such as BCL-2 inhibitor plus hypomethylating agent regimens during this time. Persistent disparities were observed in certain regions, underscoring the need for targeted interventions to improve access to optimal sepsis care and AML treatment nationwide.

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2025
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