Global, regional, and national burden of acute leukemia and its risk factors from 1990 to 2021 and predictions to 2040: findings from the global burden of disease study 2021

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Abstract

Background

Despite therapeutic advances, acute leukemia (AL) continues to impose a substantial global health burden, with persistently high incidence and mortality rates. Notably, the prediction is that the number of incidence and mortality of acute myeloid leukemia (AML) cases will continue to increase to 184,287.88 and 165,537.59, respectively, by 2040. Using Global Burden of Disease Study (GBD) 2021 data, we assessed the worldwide AL burden from 1990 to 2021, analyzing trends by sex to inform public health strategies.

Methods

To delineate the burden of AL, we reported incidence, prevalence, mortality, and disability-adjusted life year (DALY) rates at global, regional, and national levels, with these estimates including age-standardized rates (ASRs) per 100,000 population and average annual percentage changes (AAPCs) from 1990 to 2021 which were stratified by age, sex, and socio-demographic index (SDI), and computed ASRs and AAPCs using linear regression. Temporal trends were analyzed using an age-period-cohort (APC) model with intrinsic estimation (principal component regression). Risk factor attribution quantified contributions of 21 behavioral, environmental, and metabolic exposures to AL-related DALYs. For inequality assessment, we applied the Slope Index of Inequality and Concentration Index to evaluate absolute and relative disparities in AL burden across regions and countries. Future projections (2040) were modeled via a Bayesian APC framework with Integrated Nested Laplace Approximation. All statistical analyses were performed using R software (version R 4.4.1). The GATHER (Guidelines for Accurate and Transparent Health Estimates Reporting) statement provides a framework to ensure the transparency, reproducibility, and quality of health estimates reporting.

Results

Between 1990 and 2021, global ASRs of AL declined, except for acute lymphoblastic leukemia (ALL) age-standardized prevalence rates (ASPR) (AAPC 0.84, 95% CI 0.59-1.10). Case numbers rose overall, though ALL mortality and DALYs decreased. AML burden correlated positively with SDI (ρ > 0, P < 0.001), with the highest number of incident and mortality cases in Western Europe. For ALL, SDI showed positive associations with ASIR and ASPR (ρ > 0, P < 0.001) but negative correlations with ASMR and ASDALR (ρ < 0, P < 0.001), with East Asia being the most severely affected region. High body mass index (BMI), smoking, and benzene/formaldehyde exposure were key AL DALY risk factors. High BMI and smoking predominate in developed countries, and the proportion of DALYs decreases progressively as SDI decreases. Occupational exposures prevailed in developing countries. Population growth drove most absolute increases. Males bore a greater AL burden. AML risk rose with age, whereas ALL displayed bimodal peaks (< 5 and > 40 years). Notably, while ASRs in AL are projected to decline slightly and the number of ALL to decrease by 2040, the number of AML is expected to increase, with the number of incidence and mortality cases increasing by 41.56% and 27.16%, respectively.

Conclusion

As a major public health concern, despite declining ALL-related mortality and DALYs (1990–2021), AL remains a growing global health challenge, with AML cases projected to rise significantly by 2040. Region-specific intervention strategies are required: high-SDI nations should prioritize smoking cessation and metabolic control to address smoking and high BMI-related AML risks while preparing for aging populations, whereas low/middle-SDI countries urgently need enhanced pediatric ALL diagnosis, treatment capacity, and occupational safety measures. Effective mitigation demands evidence-based health planning, including resource allocation guided by projected AL burden trends and targeted policy interventions to reduce healthcare disparities.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12938-025-01403-7.

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Most cited references 31

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The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.

Daniel Arber, Attilio Orazi, Robert P. Hasserjian … (2016)

The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

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Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Gangzhen Qian, Javad Sharifi-Rad, Patrick Wen … (2024)

Summary Background Detailed, comprehensive, and timely reporting on population health by underlying causes of disability and premature death is crucial to understanding and responding to complex patterns of disease and injury burden over time and across age groups, sexes, and locations. The availability of disease burden estimates can promote evidence-based interventions that enable public health researchers, policy makers, and other professionals to implement strategies that can mitigate diseases. It can also facilitate more rigorous monitoring of progress towards national and international health targets, such as the Sustainable Development Goals. For three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has filled that need. A global network of collaborators contributed to the production of GBD 2021 by providing, reviewing, and analysing all available data. GBD estimates are updated routinely with additional data and refined analytical methods. GBD 2021 presents, for the first time, estimates of health loss due to the COVID-19 pandemic. Methods The GBD 2021 disease and injury burden analysis estimated years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries using 100 983 data sources. Data were extracted from vital registration systems, verbal autopsies, censuses, household surveys, disease-specific registries, health service contact data, and other sources. YLDs were calculated by multiplying cause-age-sex-location-year-specific prevalence of sequelae by their respective disability weights, for each disease and injury. YLLs were calculated by multiplying cause-age-sex-location-year-specific deaths by the standard life expectancy at the age that death occurred. DALYs were calculated by summing YLDs and YLLs. HALE estimates were produced using YLDs per capita and age-specific mortality rates by location, age, sex, year, and cause. 95% uncertainty intervals (UIs) were generated for all final estimates as the 2·5th and 97·5th percentiles values of 500 draws. Uncertainty was propagated at each step of the estimation process. Counts and age-standardised rates were calculated globally, for seven super-regions, 21 regions, 204 countries and territories (including 21 countries with subnational locations), and 811 subnational locations, from 1990 to 2021. Here we report data for 2010 to 2021 to highlight trends in disease burden over the past decade and through the first 2 years of the COVID-19 pandemic. Findings Global DALYs increased from 2·63 billion (95% UI 2·44–2·85) in 2010 to 2·88 billion (2·64–3·15) in 2021 for all causes combined. Much of this increase in the number of DALYs was due to population growth and ageing, as indicated by a decrease in global age-standardised all-cause DALY rates of 14·2% (95% UI 10·7–17·3) between 2010 and 2019. Notably, however, this decrease in rates reversed during the first 2 years of the COVID-19 pandemic, with increases in global age-standardised all-cause DALY rates since 2019 of 4·1% (1·8–6·3) in 2020 and 7·2% (4·7–10·0) in 2021. In 2021, COVID-19 was the leading cause of DALYs globally (212·0 million [198·0–234·5] DALYs), followed by ischaemic heart disease (188·3 million [176·7–198·3]), neonatal disorders (186·3 million [162·3–214·9]), and stroke (160·4 million [148·0–171·7]). However, notable health gains were seen among other leading communicable, maternal, neonatal, and nutritional (CMNN) diseases. Globally between 2010 and 2021, the age-standardised DALY rates for HIV/AIDS decreased by 47·8% (43·3–51·7) and for diarrhoeal diseases decreased by 47·0% (39·9–52·9). Non-communicable diseases contributed 1·73 billion (95% UI 1·54–1·94) DALYs in 2021, with a decrease in age-standardised DALY rates since 2010 of 6·4% (95% UI 3·5–9·5). Between 2010 and 2021, among the 25 leading Level 3 causes, age-standardised DALY rates increased most substantially for anxiety disorders (16·7% [14·0–19·8]), depressive disorders (16·4% [11·9–21·3]), and diabetes (14·0% [10·0–17·4]). Age-standardised DALY rates due to injuries decreased globally by 24·0% (20·7–27·2) between 2010 and 2021, although improvements were not uniform across locations, ages, and sexes. Globally, HALE at birth improved slightly, from 61·3 years (58·6–63·6) in 2010 to 62·2 years (59·4–64·7) in 2021. However, despite this overall increase, HALE decreased by 2·2% (1·6–2·9) between 2019 and 2021. Interpretation Putting the COVID-19 pandemic in the context of a mutually exclusive and collectively exhaustive list of causes of health loss is crucial to understanding its impact and ensuring that health funding and policy address needs at both local and global levels through cost-effective and evidence-based interventions. A global epidemiological transition remains underway. Our findings suggest that prioritising non-communicable disease prevention and treatment policies, as well as strengthening health systems, continues to be crucially important. The progress on reducing the burden of CMNN diseases must not stall; although global trends are improving, the burden of CMNN diseases remains unacceptably high. Evidence-based interventions will help save the lives of young children and mothers and improve the overall health and economic conditions of societies across the world. Governments and multilateral organisations should prioritise pandemic preparedness planning alongside efforts to reduce the burden of diseases and injuries that will strain resources in the coming decades. Funding Bill & Melinda Gates Foundation.

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Overweight, Obesity, and Mortality from Cancer in a Prospectively Studied Cohort of U.S. Adults

Eugenia E Calle, Carmen Rodríguez, Kimberly Walker-Thurmond … (2003)

The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites. Copyright 2003 Massachusetts Medical Society

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Author and article information

Contributors

Yayue Zhang: yayuezhang@126.com

Li Hou: houli1203@126.com

Journal

Journal ID (nlm-ta): Biomed Eng Online

Journal ID (iso-abbrev): Biomed Eng Online

Title: BioMedical Engineering OnLine

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-925X

Publication date (Electronic): 10 June 2025

Publication date PMC-release: 10 June 2025

Publication date Collection: 2025

Volume: 24

Electronic Location Identifier: 72

Affiliations

[1 ]Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, ( https://ror.org/05damtm70) Beijing, 100700 China

[2 ]Beijing University of Chinese Medicine, ( https://ror.org/05damtm70) Beijing, 100029 China

Article

Publisher ID: 1403

DOI: 10.1186/s12938-025-01403-7

PMC ID: 12150532

PubMed ID: 40495176

SO-VID: af290cab-75b1-49b9-80aa-c9da5c2580aa

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

History

Date received : 6 January 2025

Date accepted : 27 May 2025

Funding

Funded by: the Natural Science Foundation of Beijing

Award ID: 7242236

Funded by: the Leading Talents Project of Dongzhimen Hospital, Beijing University of Chinese Medicine

Award ID: CZ015

Funded by: National Administration of Traditional Chinese Medicine High level Key Discipline Construction Project of Traditional Chinese Medicine Hematology

Award ID: zyyzdxk-2023268

Funded by: the National Natural Science Foundation of China

Award ID: 82074240

Custom metadata

ScienceOpen disciplines: Biomedical engineering

Keywords: acute leukemia,epidemiology,covid-19,risk factors,global burden of disease,forecasting

Data availability: