Introduction: Acute Myeloid Leukemia (AML) remains a clinically and biologically aggressive hematologic malignancy with substantial mortality across the adult U.S. population. Although several therapeutic advancements have been made in recent years, it remains unclear as to what extent survival has improved at the population level, particularly across key demographic and geographic subgroups. The age-adjusted mortality-to-incidence ratio (AAMIR) offers a pragmatic, population-based surrogate for survival that integrates incidence and mortality trends in a unified metric.

Methods: We accessed the CDC WONDER platform's United States Cancer Statistics database for AML incidence and mortality data (1999–2021) for adults ≥20 years, stratified by year, age (20–39, 40–65, ≥65 years), gender, race/ethnicity (Non-Hispanic Whites [NHW], Non-Hispanic Blacks [NHB], Hispanics [HSP], Non-Hispanic American Natives [NHAN], Non-Hispanic Asian/Pacific Islanders [NHAPI]), region, and state. Age-Adjusted Incidence Rates (AAIR) and Age-Adjusted Mortality Rates (AAMR) per 100,000 were standardized to the 2000 U.S. Census, with AAMIR calculated annually (AAMR/AAIR) using STATA. Joinpoint Regression assessed trends, reporting Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC).

Results: Between 1999 and 2021, there were 291,049 new cases and 207,713 AML-related deaths. From 1999-2008, the AAMIR increased significantly (APC: 1.58, p<0.001*), followed by a significant decline between 2008-2011 (APC: -4.48, p=0.002*) and relative stability from 2011-2021 (APC: -0.81, p=0.15). Although, males had higher AAIRs and AAMRs than females across the study period, yet both genders exhibited AAMIR declines over time. Age significantly influenced AAMIR, with young adults (20–39y) experiencing significant improvement (AAMIR: 0.415–0.262; AAPC: –2.23, p<0.001*) followed by middle-aged adults (40–64y) (AAMIR: 0.603 to 0.487; AAPC: –0.99, p<0.001*). Older adults (≥65y) showed persistently elevated AAMIRs (0.798 to 0.808; AAPC: 0.06, p=0.74) from 1999-2021. Both NHB (AAMIR 0.736 to 0.626; AAPC: −0.27%, p=0.39) and NHW (AAMIR 0.710 to 0.684; AAPC: −0.42%, p=0.10) experienced a non-significant decline in AAMIR over time whereas HSP (AAMIR 0.557 to 0.516; AAPC: −0.79%, p=0.04), NHAPI (AAMIR 0.672 to 0.587; AAPC: −1.21%, p=0.002) and NHAN (AAMIR 0.506 to 0.507; AAPC: −2.63%, p<0.001) experienced significant improvements for the same time period.

State-level analysis revealed geographic variation in AML AAMIR trends from 1999 to 2021. Minnesota led with the greatest AAMIR reduction (0.757–0.626; AAPC: −2.26%, p=0.024), followed by Iowa (0.868–0.556; AAPC: −1.75%, p=0.079) and Florida (0.682–0.551; AAPC: −1.38%, p=0.169), while Pennsylvania showed the least progress with rising AAMIRs (0.589–0.725; AAPC: 0.39%, p=0.698), alongside California (0.691–0.680; AAPC: 0.26%, p=0.797) and Connecticut (0.580–0.639; AAPC: 0.87%, p=0.383).

Conclusions: This national analysis reveals that AML outcomes have modestly improved across the United States over the past two decades, suggesting gradual improvements in population-level survival. However, disparities remain pronounced across age, race/ethnicity and geography. Older adults, as well as NHB and NHW individuals, and residents of Pennsylvania, California, and Connecticut showed minimal progress whereas younger patients, HSP, NHAPI and NHAN patients experienced significant gains. This is a nationwide characterization of AML using AAMIR, underscoring its potential as a simple, integrative, and equity-sensitive metric for tracking longitudinal trends in cancer outcomes and guiding future interventions in public health oncology.

This content is only available as a PDF.
2025
Sign in via your Institution