Background: Acute myeloid leukemia (AML) remains a highly fatal hematologic malignancy among older adults in the United States. Despite the availability of novel therapies, the long-term epidemiological trends across demographic subgroups remain poorly defined. This study aimed to evaluate temporal trends in AML-related mortality among adults aged ≥65 years in the U.S. from 1979 to 2023, stratified by sex, race, and Census region, and to forecast mortality through 2050.Methods: AML-related deaths were identified using ICD-9 code 205.0 and ICD-10 code C92.0 from the CDC WONDER database. Age-adjusted mortality rates (AAMRs) per million were calculated for each subgroup. Joinpoint regression was used to estimate average annual percent changes (AAPCs) and significant trend shifts (APCs). To forecast mortality through 2050, Box-Cox ARIMA models were developed after stationarity testing using the ADF and KPSS tests.

Results: Between 1979 and 2023, a total of 224,418 AML-related deaths occurred among U.S. adults aged ≥65. The AAMR increased from 107.8 per million (95% CI: 103.5–112) in 1979 to 149.2 per million (95% CI: 146–152.5) in 2023. The AAPC was +0.72% (95% CI: 0.52%–0.93%; p < 0.001). Joinpoint analysis identified four distinct periods. A decline from 1979–1989 (APC –0.75%; 95% CI: –1.31% to –0.19%; p = 0.01), a sharp rise from 1989–2002 (APC +2.52%; 95% CI: 2.16%–2.88%; p < 0.001), a continued rise from 2002–2011 (APC +1.17%; 95% CI: 0.62%–1.73%; p = 0.0001), and a modest decline from 2011–2023 (APC –0.30%; 95% CI: –0.55% to –0.04%; p = 0.02).

Males exhibited significantly higher AML-related mortality rates than females, with an overall AAMR of 178.86 per million (95% CI: 171.83–184.89) compared to 98.66 per million in females (95% CI: 94.43–102.90). Regionally, The Midwest had the highest AAMR of 142.03 (95% CI: 134.04–150.02), followed by the West (132.10), Northeast (131.56), and South (123.54). All regions experienced significant long-term increases in mortality, with the Midwest exhibiting the steepest rise (AAPC: +0.82%, 95% CI: 0.50–1.19, p<0.000001).

White individuals had the highest AAMR at 136.59 per million, followed by Asian/Pacific Islanders (99.2), Black or African American individuals (92.8), and American Indian/Alaska Natives (74.4). AML mortality rates increased significantly across all racial groups. The steepest rise was observed in Black or African American individuals (AAPC:+1.29%, 95% CI: 1.06 to 1.52).

Forecasting models project a continued increase inAAMR, reaching approximately 191.4 per million by 2050 (95% CI: 157.7–225.1), suggesting a sustained disease burden despite recent declines.

Conclusion: Despite recent modest declines, AML-related mortality among U.S. adults aged ≥65 has increased significantly over the past four decades, with persistent disparities across sex, race, and region. Forecasting models project a continued upward trend, with the age-adjusted mortality rate expected to reach approximately 191.4 per million by 2050. These findings highlight the urgent need for targeted prevention strategies, improved access to novel therapies, and focused public health interventions to address the growing burden of AML in the aging population.

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2025
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