Incidence burden of AML across the US and Puerto Rico: A two-decade analysis of trends and disparities (1999-2021)

Abstract BACKGROUND: Acute myeloid leukemia (AML) is one of the most aggressive forms of hematologic malignancy of adults; its incidence increases as individuals age, and it varies markedly between racial and geographic subgroups. Previous studies have examined trends in AML mortality and survival; however, there has been less examination of trends in long-term incidence, particularly for underrepresented populations such as individuals from Puerto Rico. Understanding these patterns is tremendously important to explore disparity in AML diagnosis, inform equitable health care delivery, and develop targeted efforts around early detection for high-risk communities. RESEARCH QUESTION: What are the temporal trends and demographic disparities in the incidence of acute myeloid leukemia (AML) in the United States and Puerto Rico from 2000 to 2022? OBJECTIVES: To evaluate and compare the incidence burden of AML across the United States and Puerto Rico, stratified by age, sex, race/ethnicity, region, and urbanization, over the past two decades. METHODS: We conducted a retrospective population-based analysis using data from Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC Wonder) Database. Age-adjusted incidence rates (AAIRs) per 100,000 population were calculated using the direct method standardized to the 2000 U.S. population. Trends were analysed using Joinpoint regression to estimate annual percentage changes (APC) and average annual percentage changes (AAPC) with 95% confidence intervals. Subgroup analyses were performed based on sex, age group, race/ethnicity (including Hispanic, non-Hispanic White, non-Hispanic Black, Asian/Pacific Islander, and American Indian/Alaska Native), geographic region, and urbanization level. RESULTS: From 1999 to 2021, the age-adjusted incidence rate (AAIR) of AML showed a modest, non-significant increase with an AAPC of +0.49%, indicating relative stability in overall incidence over the two-decade period. AML incidence increased across all U.S. regions, though significance varied. The South showed a statistically significant rise (AAPC: +0.76%), while changes in the Northeast (+0.21%), Midwest (+0.50%), and West (+0.15%) were not statistically significant. A non-significant upward trend was noticed in both sexes. Females had a higher AAPC of +0.61% compared to males (AAPC: +0.25%), though neither change reached statistical significance. The incidence increased significantly in several younger and older age groups. Notable rises were seen in adolescents aged 10–14 (AAPC: +0.68%) and young adults aged 25–49, with the steepest increases among those 35–39 (AAPC: +0.93%) and 30–34 (AAPC: +0.70%). Children under 10 and individuals aged 15–24 showed stable trends. While most middle-aged and older adult groups (50–84 years) exhibited no significant changes, the 85+ age group experienced the highest rise in incidence (AAPC: +1.28%), highlighting a growing disease burden in the elderly. AML incidence increased across all racial groups, though significance varied. American Indian or Alaska Native individuals experienced the most significant rise (AAPC: +1.27%), followed by non-significant upward trends in Asian or Pacific Islanders (+0.64%), Black or African Americans (+0.67%), and Whites (+0.49%). These findings highlight a disproportionately rising burden in Indigenous populations. CONCLUSION: The incidence of AML increased in the United States and Puerto Rico from 1999 to 2021. Incidence rates increased between 2008 and 2012. People 60 years or older, men, and American Indian/Alaska Native and Asian races had the greatest burden of AML. There were also larger regional fluctuations in the South and West. While trends over recent years might suggest stabilization for some groups, the persistent demographic and geographic inequities remind us of the need for focused surveillance, early detection, and research. Keywords:Health Equity; Puerto Rico; United States; CDC WONDER; Joinpoint Regression; Cancer Surveillance; Racial Disparities; Geographic Variation; Outcomes Research