Geographic, demographic, and risk factor profiles of acute myeloid and acute lymphoblastic leukemia in the United States: Insights from the global burden of disease study 2021

Abstract Background: Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are aggressive hematologic malignancies with substantial mortality and disability. Understanding geographic, demographic, and modifiable risk factor patterns is essential for targeted prevention and resource allocation. This study characterizes the U.S. burden of AML and ALL, with a focus on age-standardized disability-adjusted life years (DALYs) attributable to specific risk factors, and evaluates temporal trends using Estimated Annual Percentage Change (EAPC) metrics. Methods: Data were obtained from the Institute for Health Metrics and Evaluation (IHME) GBD 2021 Results Tool. Age-standardized incidence, prevalence, mortality, and DALY rates were analyzed for each state, stratified by sex and age group. Age-standardized DALYs attributable to smoking, high body mass index (BMI), and occupational carcinogen exposure were extracted and ranked by percentage contribution. EAPCs with 95% confidence intervals (CIs) were calculated to evaluate temporal trends. Descriptive statistics were performed using Microsoft Excel. Results: For AML, the highest age-standardized incidence rates occurred in Kentucky (4.72), Michigan (4.57), and Nebraska (4.53), and the lowest in the District of Columbia (2.70), Washington (2.86), and California (3.12). Prevalence was highest in Michigan (8.97), New Jersey (7.68), and Georgia (7.61). For ALL, incidence peaked in Arizona (2.11), Minnesota (1.90), and California (1.87), while prevalence was highest in Arizona (14.17), Minnesota (13.67), and California (12.75). Male predominance was observed for most incidence, prevalence, mortality, and DALY rates, except in certain younger and older age groups. EAPC analysis showed that for AML, incidence increased slightly (0.38%, 95% CI: 0.14 to 0.62), prevalence rose (0.62%, 95% CI: 0.33 to 0.92), while death rates remained stable (0.03%, 95% CI: –0.17 to 0.24). DALY rates declined modestly (–0.49%, 95% CI: –0.67 to –0.32). In contrast, ALL showed decreases across all measures: incidence (–0.78%, 95% CI: –0.98 to –0.58), prevalence (–0.43%, 95% CI: –0.70 to –0.16), death rate (–1.55%, 95% CI: –1.63 to –1.46), and DALY rate (–1.88%, 95% CI: –1.97 to –1.78). Risk factor analysis using age-standardized DALYs found smoking to be the leading contributor for both AML and ALL in all states, followed by high BMI and occupational carcinogens. For AML, smoking-attributable DALY burden was highest in Kentucky (20.07%), Nevada (18.50%), and West Virginia (18.44%). High BMI-attributable DALYs were greatest in West Virginia (13.13%), Kentucky (12.78%), and Ohio (12.70%). Occupational carcinogen-attributable DALYs were highest in Vermont (1.02%), South Dakota (0.99%), and North Dakota (0.98%). For ALL, smoking-related DALYs peaked in Kentucky (7.90%), West Virginia (7.38%), and Maine (7.24%), while high BMI burden was highest in West Virginia (8.96%), Ohio (8.58%), and Kentucky (8.53%). Occupational carcinogen-related DALYs were highest in New Hampshire (1.21%), Vermont (1.19%), and Maine (1.18%).Conclusion: This analysis highlights marked geographic variation in AML and ALL burden across the U.S., with higher incidence and prevalence in specific states and male predominance across most metrics. Temporal trends show modest increases in AML incidence and prevalence, stability in mortality, and slight declines in DALYs, while ALL demonstrates consistent declines across all measures. Smoking and high BMI remain the dominant modifiable risk factors, with occupational exposures contributing smaller yet important burdens in certain states. These findings support targeted state-level interventions, including tobacco cessation, obesity prevention, and workplace safety programs, coupled with early detection and improved access to care.