Temporal trends in mortality due to Acute Myeloid Leukemia and sepsis in u.S. adults aged ≥25 years (1999–2023): A CDC wonder database analysis

Abstract Introduction: Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy affecting approximately 22,000 individuals annually in the United States. It ranks as the 15th leading cause of cancer-related deaths, accounting for 1.75% of all cancer mortality. AML patients are particularly vulnerable to sepsis due to profound neutropenia and immunosuppression from both the malignancy and its intensive treatment. The incidence of sepsis in AML patients is significantly higher than in non-AML populations (16% vs. 4%), and these patients experience a 1.5-fold increased mortality risk from sepsis. Despite its clinical relevance, trends in mortality from the combined burden of AML and sepsis remain understudied. This study utilizes the CDC WONDER database to evaluate national trends and disparities in AML-related sepsis mortality from 1999 to 2023 across various demographic and geographic subgroups. Methods: We conducted a retrospective analysis of U.S. death certificate data from the CDC WONDER database for adults aged ≥25 years between 1999 and 2023. AML and sepsis were identified using ICD-10 codes C92.0 and A41–A42, respectively. Deaths in which both AML and sepsis were listed as contributing causes were included. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated. Temporal trends were assessed using Joinpoint regression to compute Annual Percent Changes (APCs). Subgroup analyses were performed by sex, race/ ethnicity, geographic region, urbanization level, and state. Results: A total of 28,545 deaths were attributed to the combined diagnosis of AML and sepsis. The overall AAMR increased from 0.47 in 1999 to 0.51 in 2020, with an average annual percent change (AAPC) of +0.48% (95% CI: 0.07 to 0.89; p = 0.023). Throughout the study period, males consistently had higher AAMRs than females (1999: 0.61 vs. 0.40; 2023: 0.65 vs. 0.38). Among racial/ethnic groups, Non-Hispanic Black individuals had the highest overall AAMR (0.52), followed closely by Non-Hispanic White (0.51), Non-Hispanic Asian or Pacific Islander (0.46), and Hispanic or Latino populations (0.42). Regionally, the Northeast reported the highest AAMR (0.53), followed by the South (0.50), with both the Midwest and West reporting an AAMR of 0.49. Non-metropolitan areas had slightly higher AAMRs compared to metropolitan areas (0.50 vs. 0.49). States in the top 90th percentile for AML-sepsis mortality included Mississippi, Arkansas, California, Pennsylvania, and Texas. Conclusion: This 24-year national analysis reveals a modest but statistically significant increase in mortality from the combined burden of AML and sepsis among U.S. adults, alongside notable and persistent disparities by sex, race, geography, and urbanization status. The higher mortality burden in males, non-Hispanic Black and White populations, rural communities, and the Northeast underscores systemic vulnerabilities that may be driven by delays in diagnosis, limited access to specialized care, and inadequate sepsis management in immunocompromised patients. To reduce excess mortality in this high-risk population, equity-focused strategies are urgently needed. These include early identification and aggressive management of sepsis, improvements in supportive care during AML treatment, and targeted public health interventions aimed at underserved regions and populations.