Introduction Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by clonal proliferation of abnormal myeloid precursors in bone marrow, leading to impaired hematopoiesis and high early mortality. Although treatment options have expanded over the past two decades, AML remains associated with significant morbidity. Outcomes can vary based on clinical and sociodemographic factors. In this study, we aim to examine long-term trends and disparities in AML-related deaths in the U.S. adult population aged 25 and older from 1999 to 2023.

Methods We utilized the CDC WONDER database to extract data on mortality for AML in the U.S. population (age ≥ 25 years). Data was stratified based on age, sex, census, and race/ethnicity. Age was stratified into three groups: older adults (≥ 65 years), middle-aged adults (45-64 years), and younger adults (25-44 years). Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population. Joinpoint regression software was used to estimate trends in mortality by calculating the average annual percentage changes (AAPCs) and annual percentage changes (APCs).

Results From 1999 to 2023, a total of 236593 AML-related deaths were recorded in our study population. Overall, the average AAMR was 4.25, which increased significantly from 3.76 in 1999 to 4.22 in 2023 (AAPC: 0.49, p-value: 0.001). A significant increase in AAMR was observed from 3.76 in 1999 to 4.16 in 2001 (APC: 4.81, p-value: 0.001), followed by a non-significant rise to 4.46 by 2009 (APC: 0.69, p-value: 0.05) and finally a significant reduction to 4.22 by 2023 (APC: -0.22, p-value: 0.02).

A gender-based study reported total deaths in adult males (n=134090) and adult females (n=102503) from 1999 to 2023. Males had a higher average AAMR (5.52) than females (3.32). Significant increase in AAMR was observed in males from 4.81 in 1999 to 5.42 in 2023 (AAPC: 0.53, p-value: 0.001), and females showed a non-significant increase from 3.05 in 1999 to 3.21 in 2023 (AAPC: 0.15, p-value: 0.17).

Age-based analysis showed that older adults had a higher average AAMR (15.9) than middle-aged adults (2.55) and younger adults (0.58). Significant increase was observed in older adults from 13.24 in 1999 to 16.5 in 2023 (AAPC: 0.91, p-value: 0.001), while in middle-age adults, significant reduction occurred from 2.66 in 1999 to 2.2 in 2023 (AAPC: -0.85, p-value: 0.008) and non-significant reduction was observed in young adults from 0.56 in 1999 to 0.51 in 2023 (AAPC: -0.61, p-value: 0.07). Overall, about 171976 deaths in older adults, followed by 52379 in middle-aged adults, and 12238 in young adults, occurred during this study period.

Census-based study showed the Midwest had the highest average AAMR (4.68), followed by the Northeast (4.28), the West (4.14), and the South (4.04). The highest significant increase was seen in the Midwest (AAPC: 0.54, p-value: 0.01), followed by the South (AAPC: 0.36, p-value: 0.02), the Northeast (AAPC: 0.32, p-value: 0.03), and a non-significant increase in the West (AAPC: 0.22, p-value: 0.09).

Race/Ethnicity-based analysis showed non-Hispanic (NH) White had the highest average AAMR (4.56), followed by NH Black/African American (3.41), NH Asian/Pacific Islander (2.97), and Hispanic/Latino (2.75). The highest significant increase in AAMR was observed in NH White from 3.97 in 1999 to 4.56 in 2023 (AAPC: 0.62, p-value: 0.001) and in NH Asian/Pacific Islander from 2.92 in 1999 to 2.89 in 2023 (AAPC: 0.62, p-value: 0.03). This was followed by NH Black/African American from 3.13 in 1999 to 3.58 in 2023 (AAPC: 0.54, p-value: 0.001) and Hispanic/Latino from 2.55 in 1999 to 2.87 in 2023 (AAPC: 0.35, p-value: 0.03). Highest total deaths were in NH White (n=196089), followed by NH Black/African American (n=18449), Hispanic/Latino (n=13506), and NH Asian/Pacific Islander (n=7136).

Conclusion Over the past two decades, there has been a significant increase in mortality rates related to AML in the U.S., with notable disparities among demographic groups. The rise in mortality has been particularly pronounced among males and older adults. Additional high-risk groups include White individuals and those living in the Midwest. An analysis of trends within each demographic category has revealed distinct patterns, highlighting variations in mortality trajectories among subgroups. Addressing the specific challenges faced by different groups is essential for improving treatment outcomes in the future.

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2025
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