Incidence patterns of Acute Myeloid Leukemia in the United States from 1999 to 2021: Analysis by age, sex, and race/ethnicity

Abstract Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with variable incidence by age, sex, and race. Timely characterization of incidence trends is critical for understanding disease burden and addressing disparities. Methods: We analyzed data from the United States Cancer Statistics (USCS) Public Use Database from 1999 to 2021 to identify incident cases of acute myeloid leukemia (AML) in all age groups. Incidence rates were age-adjusted to the 2000 U.S. standard population and reported per 100,000 persons. Age group frequencies were assessed, and trend analyses were stratified by sex and race/ethnicity. Joinpoint regression was used to estimate annual percent change (APC) for each trend segment and average annual percent change (AAPC) over the entire study period, with 95% confidence intervals (CIs). Results: A total of 304,775 AML deaths were identified among 7.1 billion person-years. Age-adjusted incidence rate (AAIR) increased from 3.68 (95% CI, 3.61–3.75) in 1999 to 4.18 (95% CI, 4.12–4.25) in 2021. The incidence was higher in males (AAIR 5.01 in 2021) than in females (3.55) and highest among non-Hispanic Whites (4.33) compared to non-Hispanic Blacks (3.62), Hispanics (3.64), and Asians/Pacific Islanders (3.33). Crude incidence rates were lowest among children and young adults (<1 per 100,000 person-years), but rates increase sharply after age 60, to more than 20 per 100,000 in individuals aged 75 and older. From 1999 to 2021, AML incidence showed a modest overall increase (AAPC +0.49%; 95% CI, 0.31–0.66). Joinpoint analysis revealed three distinct trends: an initial decrease (APC –0.57%;1999–2008), a sharp rise (APC +6.37%; 2008–2011), followed by relative stabilization (APC–0.27%; 2011–2021). All groups experienced a transient increase in 2008–2011 or 2007–2012, after which rates plateaued or declined slightly. Conclusion: The incidence of acute myeloid leukemia in the United States increased modestly from 1999 to 2021, with persistent disparities by sex and race/ethnicity. Incidence remained low in younger age groups but rose sharply with advancing age, highlighting a disproportionate burden among older adults. These findings underscore the need for continued surveillance, targeted prevention strategies, and further research into the underlying causes of demographic disparities in AML incidence.