The Global Burden of Chronic Lymphocytic Leukemia and Its Attributable Factors in 204 Countries and Territories: Findings from the Global Burden of Disease 2021 Study and Projections to 2035

Background: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, yet its epidemiology is evolving globally. Despite a modest decline in age-standardized incidence rates, improvements in diagnostic capabilities and population ageing have resulted in a substantial rise in the absolute burden of CLL. Methods: We conducted a comprehensive analysis of data from the Global Burden of Disease (GBD) 2021 study, spanning 204 countries and territories between 1990 and 2021. Standardized metrics—including incidence, prevalence, mortality, and disability-adjusted life years (DALYs)—were used to assess temporal and spatial trends, while risk factor contributions were evaluated across socio-demographic index (SDI) strata, age groups, and sex. Bayesian age–period–cohort models were employed to project future trends under a business-as-usual scenario through 2035. Results: Between 1990 and 2021, the absolute number of CLL cases increased from 57,961 (95% UI: 53,100–61,681) to 98,330 (95% UI: 98,330–132,718)—an approximate 70% rise—while the age-standardized incidence rate (ASIR) declined from 1.55 (95% UI: 1.41–1.64) to 1.39 (95% UI: 1.16–1.56) per 100,000 population. Similarly, deaths increased from 29,278 to 45,573, despite a fall in the age‐standardized death rate from 0.83 to 0.55 per 100,000. In high-SDI regions, rigorous exposure assessments indicated that modifiable risk factors, notably tobacco use and elevated BMI, contributed up to 22% of the burden, compared with contributions below 3% in low-SDI regions. Bayesian projections suggest that, by 2035, the ASIR will rise from 2.141 (95% UI: 2.086–2.197) to 2.207 (95% UI: 1.859–2.554) per 100,000, with incident cases increasing by 16.5% from 168,993 (95% UI: 164,567–173,419) to 196,866 (95% UI: 165,861–227,871). Conclusion: Our findings reveal a paradoxical epidemiological landscape in which improvements in diagnostic sensitivity and therapeutic interventions coincide with a rising absolute burden of CLL. These data underscore the urgent need for tailored public health strategies—focusing on early detection, risk factor mitigation, and long-term management—to address regional disparities and the evolving challenges posed by CLL worldwide.