Abstract
BACKGROUND: Acute lymphoblastic leukemia (ALL) remains a major public health challenge, yet its global burden and epidemiological trends are inadequately characterized. This study evaluates the global burden of ALL from 1990 to 2021 and projects trends through 2040. METHODS: Using data from the Global Burden of Disease (GBD) Study 2021, we analyzed prevalence, incidence, mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) for ALL, stratified by time, region, age, and Socio-Demographic Index (SDI). Advanced methods included estimated annual percentage change (EAPC), Joinpoint regression, decomposition and frontier analyses, and Bayesian Age-Period-Cohort (BAPC) modeling to quantify trends, inequalities, and projections. RESULTS: In 2021, ALL caused 386,813 prevalent cases globally (10.3% increase since 1990) and 71,221 deaths (41.8% decline). Age-standardized prevalence rate (ASPR) rose from 4.1 to 5.4 per 100,000 (EAPC = 1.4), while mortality rate (ASMR) decreased significantly (EAPC = - 1.73). High SDI regions exhibited the highest ASPR (16.1 vs. 1.3 per 100,000 in low-SDI areas) but lower ASMR (0.5 vs. 1.3) and DALY rates (23.7 vs. 47.9). A bimodal age distribution peaked in children < 5 years (21.5 per 100,000), with male predominance across ages. Modifiable risks included high BMI (5.8% of global deaths) and smoking (15.4% in high-income North America). Health inequalities widened: the slope index of inequality for prevalence increased from 3.22 to 4.23 (1990-2021), and ASDR disparity reached - 30.97. Frontier analysis highlighted untapped ASDR reduction potential in low-SDI nations (97.17-136.34 per 100,000). Projections suggest a 50% global ASPR decline by 2040 (2.84 per 100,000), though regional disparities persist. CONCLUSION: The global ALL burden reflects progress and disparity: high-SDI regions face rising prevalence and aging-related challenges despite mortality declines, while low-SDI areas grapple with entrenched inequities. Age- and sx-specific patterns, alongside modifiable risks, necessitate targeted prevention and equity-driven policies.