Demographic and regional trends and disparities in leukemia mortality in the United States (1999–2022): A comparative analysis of underlying and contributing cause models of death.

e18517 Background: Leukemia, a hematological malignancy, ranks as the sixth leading cause of cancer-related deaths in males and seventh in females in the U.S. Advances in treatments, including tyrosine kinase inhibitors, monoclonal antibodies, and CAR T-cell therapy, have improved survival rates. However, limited research has examined leukemia as a contributing cause of death or its trends in the post-COVID-19 era. This study evaluates U.S. leukemia mortality trends from 1999 to 2022, focusing on disparities by sex, race, and region, and comparing leukemia as an underlying versus contributing cause of death. Methods: Mortality data from the CDC WONDER system were analyzed for leukemia listed as the underlying and contributing cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated, standardized to the 2000 U.S. population, and stratified by sex, race, and region. Joinpoint regression was used to analyze trends and annual percent changes (APCs). Statistical significance was defined as p < 0.05. Results: Between 1999 and 2022, 383,730 leukemia deaths were reported as the underlying cause and 474,481 as a contributing cause. AAMRs for underlying-cause deaths declined from 5.3 (95% CI: 5.2–5.4) in 1999 to 4.5 (95% CI: 4.5–4.6) in 2022 (APC = -0.79%, p < 0.001). Contributing-cause AAMRs also declined from 6.9 (95% CI: 6.7–7.1) in 1999 to 5.8 (95% CI: 5.7–5.9) in 2018 (APC = -0.68%, p < 0.001), but reversed post-2018, rising to 6.1 (95% CI: 6.0–6.2) by 2022 (APC = 2.43%, p = 0.006). Males consistently had higher AAMRs than females. In 1999, male and female AAMRs were 6.8 (95% CI: 6.7–7.0) and 4.0 (95% CI: 3.9–4.1), respectively, declining to 4.3 (95% CI: 4.1–4.3) and 3.2 (95% CI: 3.1–3.3) by 2022. Whites had the highest AAMRs (5.3 in 1999 to 4.5 in 2022, APC = -0.81%, p < 0.001), while American Indian/Alaska Natives had the lowest (2.5 in 1999 to 1.6 in 2022, APC = -1.47%, p < 0.001). Geographic disparities persisted, with the Midwest reporting the highest underlying-cause AAMRs (5.5 in 1999 to 4.7 in 2022, APC = -0.77%, p < 0.001). Notably, Contributing-cause AAMRs in the South and West increased significantly post-2018 (APC = 3.32%, p < 0.01; APC = 3.20%, p < 0.01). Conclusions: The decline in underlying-cause AAMRs highlights advancements in leukemia treatment. The increase in contributing-cause mortality post-2018 suggests a growing comorbidity burden, possibly influenced by COVID-19. Continued surveillance and targeted interventions are vital to address disparities and improve outcomes.