Introduction
Leukemia comprises a heterogeneous group of more than 30 lymphoid and myeloid malignancies classified under ICD-10 codes C91–C95, affecting both children and adults worldwide1. The four major subtypes—acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML)—exhibit distinct epidemiological profiles, risk factors, and outcomes. This review synthesizes data from major cancer registries and population-based studies to characterize the global burden, temporal trends, and demographic patterns of leukemia over the past decade.
Methods and Data Sources
This narrative review integrates data from authoritative sources including IARC GLOBOCAN 202291011, the Global Burden of Disease (GBD) Study 2017–201912131415, the United States Surveillance, Epidemiology, and End Results (SEER) Program2, EUROCARE-618, China's National Cancer Registry21, and regional cancer registries467. Age-standardized rates (ASR) per 100,000 population were calculated using the World Health Organization (WHO) standard population. Temporal trends were assessed using annual percent change (APC) or estimated annual percentage change (EAPC) from joinpoint regression analyses where available.
Epidemiology: Incidence and Prevalence
Global Burden
In 2022, GLOBOCAN estimated 486,777 new leukemia cases globally (2.4% of all cancers), with 277,824 cases in males and 208,953 in females91011. This represents an increase from the 437,000 cases reported in 20181. The global age-standardized incidence rate was 6.2 per 100,000 in males and 4.4 per 100,000 in females91011. Leukemia prevalence reached 2.43 million cases globally in 2017 (95% uncertainty interval [UI] 2.19–2.59 million), with an age-standardized prevalence rate of 32.26 per 100,000 (95% UI 29.02–34.61)12.
Subtype Distribution
Population-based data from the United Kingdom Haematological Malignancy Research Network (2004–2016, n=29,329 cases) revealed that chronic lymphocytic leukemia (CLL) is the largest diagnostic category among leukemias, followed by myeloproliferative neoplasms, acute myeloid leukemias, and myelodysplastic syndromes1. Acute lymphoblastic leukemia (ALL), notably B-cell ALL, predominates in children younger than 15 years (representing <4% of total leukemia cases), while CLL, myeloproliferative neoplasms, and AML are far more common at older ages1.
Regional Variation
United States
The SEER database (2018–2022) reported an overall age-adjusted incidence rate of 14.4 per 100,000 persons per year, with significant sex disparity (males 18.2 per 100,000, females 11.3 per 100,000)2. Racial and ethnic variation was pronounced, with non-Hispanic White males showing the highest incidence (20.3 per 100,000) compared with non-Hispanic Asian/Pacific Islander males (10.2 per 100,000)2. The median age at diagnosis was 68 years, with 26.1% of cases occurring in the 65–74 age group2.
China
Based on 2019 National Cancer Registry data covering 628 million people, China reported 43,275 new acute leukemia cases annually, with age-standardized incidence and mortality rates of 2.83 and 1.51 per 100,000, respectively21. AML was the most common acute leukemia at every age, with an age-standardized incidence rate of 1.24 per 100,000 in 2019, peaking at 6.26 per 100,000 in the 75–79 age group21. CML incidence ranged from 0.7–0.9 per 100,000, while CLL incidence (0.3–0.4 per 100,000) was approximately one-tenth that of Caucasian populations21.
Latin America
In Recife, Brazil (1998–2007), childhood leukemia incidence was 41.1 per million children aged 0–14 years, with peak incidence at ages 1–4 years (78.3 per million)6. In Mexico City (2007–2014), the median age of leukemia diagnosis was 38 years, with ALL showing the youngest mean age (32.6 years) and CLL the oldest (64.8 years)7.
Pediatric versus Adult Patterns
Childhood ALL demonstrates distinct racial/ethnic patterns. In California (1990–2012), Hispanic children showed higher ALL incidence (standardized rate ratio [SRR] 1.32) compared with non-Hispanic White children, while African American children had lower incidence (SRR 0.55)4. Among adolescents and young adults in the Nordic countries, AML incidence increased from 4.9 per million per year at ages 10–14 to 6.9 per million per year at ages 19–3027.
Temporal Trends
Incidence Trends
In the United States, leukemia incidence showed a modest decline with an APC of −0.5% during 2013–20222. Globally, the age-standardized prevalence rate increased slightly (EAPC +0.22%, 95% CI 0.13–0.31, P<0.01) from 1990 to 2017, despite declining age-standardized incidence rates12.
Subtype-specific trends revealed divergent patterns. For CML globally, incident cases increased 54.1% from 42.7×10³ in 1990 to 65.8×10³ in 2019, yet age-standardized incidence rates declined weakly (EAPC −1.04)13. In China, ALL demonstrated the fastest growth among hematologic malignancies, with age-period-cohort analysis revealing net annual increases of 7.1% in males and 7.5% in females; projections indicate that age-standardized incidence rates will surge 64% in males and 75% in females between 2019 and 202821.
Among California children (1990–2012), ALL incidence increased (overall APC +1.1%), with particularly steep increases in African American males (APC +2.8%), Asian/Pacific Islander males (APC +1.9%), and Hispanic females aged 15–19 years (APC +1.9%)4.
Mortality Trends
United States mortality declined more substantially than incidence, with an APC of −1.8% during 2014–2023, resulting in an age-adjusted death rate of 5.8 per 100,000 persons per year2. For CML specifically, age-standardized death rates and disability-adjusted life years (DALYs) declined dramatically (EAPC −2.55 and −2.69, respectively) from 1990 to 201913. Joinpoint analysis revealed particularly steep declines in high-sociodemographic index (SDI) regions around 2000 (age-standardized death rate EAPC −7.502 during 1998–2005), reflecting the transformative impact of tyrosine kinase inhibitor (TKI) therapy13.
Demographics and Risk Factors
Age and Sex Patterns
Male predominance is evident across the full age spectrum and major diagnostic subtypes12, with notable exceptions including myelodysplastic syndrome with deletion of chromosome 5q (female predominance)1. CML demonstrates the steepest sex gradient (male-to-female ratio 2:1 in China)21, while CLL shows a male-to-female ratio of 1.5–1.621.
Genetic Predisposition
Down syndrome, Fanconi anemia, and Li-Fraumeni syndrome confer significantly elevated leukemia risk, though comprehensive population-attributable fractions were not quantified in the retrieved materials.
Environmental and Occupational Exposures
For CML, GBD 2019 quantified four modifiable risk factors contributing to DALYs: smoking (12.2%), high body mass index (5.0%), occupational benzene exposure (0.9%), and occupational formaldehyde exposure (0.3%)13. High body mass index showed an increasing proportional contribution from 1990–201913. Provincial heterogeneity in China was most pronounced for AML, with steel- and petrochemical-heavy provinces (Guizhou, Gansu, Hebei) showing age-standardized incidence rates 4–5 times the national average21.
Globally, leukemia burden attributable to high body mass index increased from 9.35 thousand deaths in 1990 to 21.73 thousand in 2019, with an age-standardized death rate of 0.27 per 100,000 (EAPC +0.34)25.
Infectious Associations
Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million people globally, with approximately 5% developing adult T-cell leukemia/lymphoma (ATL)26. High proviral load (>4% of peripheral blood mononuclear cells), age >60 years, and oligoclonality index >0.77 identify high-risk individuals26. Whole-genome sequencing identified 10 major oncogenic drivers, with CIC-ATXN1 complex mutations present in 53% of ATL cases26.
Socioeconomic and Racial/Ethnic Disparities
In the United States, Black patients demonstrate the worst five-year survival rates across most leukemia subtypes and demographic strata5. In China, rural CLL patients experience a 1.3-fold higher 24-month treatment failure rate compared with urban patients21. High-SDI regions achieved greater mortality reductions than lower-SDI regions, though lower-SDI countries experienced the highest absolute deaths and DALYs131415.
Disease Burden: Mortality, DALYs, and Quality of Life
Mortality and Survival
Global leukemia mortality in 2022 was 305,033 deaths (3.1% of all cancer deaths), with males accounting for 173,063 deaths and females 131,97091011. United States five-year relative survival improved substantially from 33.3% in 1975 to 67.8% in 2015–20212. Subtype-specific survival in China showed marked advances: pediatric ALL survival increased from 72% to 86%, approaching Western rates of 88–91%; adult ALL survival increased from 24% to 38%; and CML ten-year overall survival exceeded 85%21.
Disability-Adjusted Life Years
Globally in 2017, leukemia accounted for substantial DALYs, with pronounced burden in populations aged ≥70 years for CML13. CML DALYs declined from 1990 to 2019 (EAPC −2.69), while AML and ALL demonstrated upward trends in both age-standardized death rates and DALYs (EAPC for DALYs: AML +1.18, ALL +1.34)25. The highest 2019 age-standardized DALY rates for BMI-attributable leukemia were observed in high-income North America (7.73 per 100,000)25.
Quality of Life
Systematic reviews of health-related quality of life (HRQoL) in AML identified fatigue as the most problematic symptom domain irrespective of treatment status30. HRQoL declined shortly after diagnosis or treatment initiation and recovered over time, with superior outcomes among AML survivors compared with individuals on active treatment30. In CML, long-term bosutinib therapy maintained HRQoL as measured by EuroQol 5-Dimensions (EQ-5D) and Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), with stable utility scores and achievement of minimally important differences in emotional well-being and total scores2931.
Limitations
Several limitations affect the interpretation of global leukemia epidemiology. Many countries lack high-quality cancer registration systems, and diagnostic challenges associated with identifying various leukemia subtypes, coupled with inconsistent WHO classification implementation, complicate global variation and trend analysis1. Even among countries with robust registries, policies for disease progression and transformation differ (e.g., SEER versus European Network of Cancer Registries), affecting comparability1. Registry completeness varies substantially between high-income and low- and middle-income countries, potentially leading to underestimation of true burden in resource-limited settings. Subtype-specific data for ALL and AML across all regions remain incomplete in the retrieved materials. Quality-of-life data are limited primarily to CML and AML, with significant evidence gaps for ALL and CLL.
Conclusions
Leukemia represents a substantial and evolving global health challenge, with nearly 487,000 new cases and 305,000 deaths annually. While mortality rates have declined substantially in high-income regions—driven by therapeutic advances such as TKI therapy for CML—absolute case numbers continue to rise due to population growth and aging. Marked disparities persist across sociodemographic strata, racial/ethnic groups, and geographic regions, with lower-SDI countries experiencing increasing disease burden. Modifiable risk factors including smoking, obesity, and occupational exposures account for measurable proportions of burden. Enhanced cancer registry coverage, improved diagnostic standardization, and expanded access to effective therapies remain critical priorities for reducing the global leukemia burden.