Rising mortality from Acute Myeloid Leukemia attributable to tobacco use in the United States, 1999–2020: A CDC wonder analysis

Abstract Background: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with multifactorial etiology, in which environmental carcinogens such as tobacco have a recognized leukemogenic role. Tobacco constituents can induce DNA damage, chromosomal aberrations, and impaired marrow function, increasing AML incidence and potentially influencing mortality outcomes. Despite declining smoking prevalence in the U.S., the mortality burden attributable to tobacco use in AML remains poorly quantified across demographic and geographic subgroups. Methods: Mortality data for AML with tobacco use listed as a multiple cause of death were extracted from the CDC WONDER Underlying Cause of Death database (1999–2020). Deaths were filtered using ICD-10 codes for AML (UCD) and tobacco use (MCD). Annual counts, crude rates, and annualized percentage change (APC) in deaths were calculated overall and stratified by U.S. Census region, state, 2013 urbanization categories, 10-year age groups, sex, Hispanic origin, and race. APC was calculated using log-linear regression to capture temporal trends. Results: From 1999 to 2020, there were 4,448 deaths, rising from 13 in 1999 to 447 in 2020, corresponding to an APC of +18.35%. By Census region, APC was highest in the Midwest (+16.64%), followed by the South (+14.43%), Northeast (+12.58%), and West (+11.85%). State-level analysis identified steep increases in Kentucky (+14.87%), Michigan (+9.13%), Texas (+6.86%), North Carolina (+5.98%), and Washington (+5.96%), with declines in Wisconsin (−1.64%), New Jersey (−2.82%), Missouri (−4.28%), Minnesota (−12.55%), and Arizona (−15.14%). By urbanization, APC was greatest in Medium Metro areas (+14.50%), followed by Large Central Metro (+12.28%), Small Metro (+10.71%), Noncore (+10.62%), Large Fringe Metro (+10.51%), and Micropolitan areas (+8.16%). APC by age group was highest in 75–84 years (+15.24%), followed by 65–74 (+13.25%), 55–64 (+11.48%), 85+ (+9.59%), and 45–54 (+1.70%). Sex-specific APC was +17.60% in males and +13.10% in females. By ethnicity, APC was +18.59% among non-Hispanic and +1.39% among Hispanic populations. Racially, APC was +18.31% in White and +9.31% in Black or African American populations. Conclusion: Mortality due to AML with tobacco use as a contributing cause has risen sharply over two decades, with the steepest increases in the Midwest, certain southern states, and Medium Metro areas, particularly among older, non-Hispanic White males. These findings emphasize the importance of integrating AML-specific risk messaging into tobacco cessation programs, prioritizing high-burden geographic areas, and strengthening policy-driven prevention strategies. Improved tobacco control, combined with targeted surveillance and early hematologic evaluation in high-risk groups, may help reduce future mortality burden.