Abstract Introduction: Leukemia, a heterogeneous group of hematologic malignancies, has

established associations with modifiable risk factors such as tobacco use. Despite the

widespread implementation of tobacco control measures over the past three decades,

disparities persist in tobacco-attributable leukemia mortality across sex and socio-

demographic strata. This study aimed to quantify and compare long-term global and regional

trends in mortality due to tobacco-associated leukemia between 1990 and 2021, with a focus

on sex-based and income-level disparities.

Methods: We obtained age-standardized mortality rates (ASMRs) for leukemia attributable

to tobacco use from the Global Burden of Disease (GBD) 2021 dataset for 204 countries and

territories. ASMRs were analyzed for the years 1990 and 2021 and stratified by sex (male,

female, both) and socio-demographic index (SDI) regions (high, high-middle, middle, low-

middle, low). Temporal trends were assessed using Average Annual Percent Change

(AAPC) with corresponding 95% confidence intervals (CI). Additionally, univariate linear

regressions by location were conducted to quantify associations between time and mortality.

Results: Globally, tobacco-related leukemia mortality decreased substantially between 1990

and 2021. The overall ASMR declined from 0.64 to 0.40 per 100,000 population (AAPC:

–1.51%; 95% CI: –1.59 to –1.43). Sex-disaggregated data revealed a more favorable

reduction in females (from 0.23 to 0.12; AAPC: –2.25%; 95% CI: –2.41 to –2.09) compared

to males (from 1.20 to 0.77; AAPC: –1.45%; 95% CI: –1.51 to –1.39), suggesting persistent

gender disparities in tobacco exposure and/or access to care. These trends were statistically

significant (p < 0.001), and global univariate regression confirmed a significant negative

slope (–0.0088; p = 0.021).

Marked regional differences emerged by SDI status. High-SDI countries experienced the

steepest declines in mortality. In these regions, ASMRs dropped from 1.16 to 0.69 among

both sexes combined (AAPC: –1.70%; 95% CI: –1.80 to –1.61), with females improving from

0.56 to 0.31 (AAPC: –1.90%; 95% CI: –2.03 to –1.76) and males from 2.07 to 1.17 (AAPC:

–1.88%; 95% CI: –1.96 to –1.80). The associated regression slope (–0.0183) was

statistically significant (p = 0.0014), with an R² of 0.10, indicating a strong temporal

association.

High-middle SDI regions showed moderate progress: ASMRs declined from 0.62 to 0.45

among both sexes (AAPC: –0.99%; 95% CI: –1.10 to –0.88). Reductions were steeper in

females (0.12 to 0.07; AAPC: –1.32%; 95% CI: –1.55 to –1.09) than in males (1.40 to 0.96;

AAPC

–1.19%; 95% CI: –1.29 to –1.09). However, regression slopes were not statistically

significant (p = 0.18), suggesting heterogeneous trends within this group.

Low-SDI regions, in stark contrast, exhibited minimal improvements. Between 1990 and

2021, ASMRs decreased marginally from 0.098 to 0.074 (AAPC: –1.01%; 95% CI: –1.10 to

–0.91), with male mortality decreasing from 0.17 to 0.12 (AAPC: –1.22%; 95% CI: –1.32 to

–1.13) and female rates from 0.037 to 0.027 (AAPC: –0.88%; 95% CI: –1.04 to –0.72).

However, the regression slope (–0.00084) was not statistically significant (p = 0.17), and the

effect size (R² = 0.02) suggested only a weak temporal association.

Middle and low-middle SDI countries also demonstrated underwhelming progress. In low-

middle SDI settings, the combined-sex ASMR dropped from 0.21 to 0.16 per 100,000, with a

weak negative slope (–0.0012; p = 0.43), and an AAPC of –0.83% (95% CI: –0.95 to –0.71).

These results highlight stagnation and growing inequities in health burden mitigation.

Conclusion: From 1990 to 2021, global mortality due to tobacco-attributable leukemia

significantly declined, with the greatest improvements seen in high-SDI countries and among

females. However, regions with lower income levels lagged, showing minimal or no

significant decline in mortality despite decades of global tobacco control efforts. The

pronounced disparities by sex and socioeconomic status underscore the need for context-

specific, equity-focused tobacco cessation initiatives and leukemia screening programs,

especially in underserved populations. Without urgent intervention, the global burden of

leukemia attributable to tobacco may continue to disproportionately affect those with the

fewest resources and weakest health infrastructure.

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2025
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