Epidemiological Trends of Acute Lymphoid Leukemia in Individuals Younger Than 20 Years across 204 Countries and Territories from 1990-2021: A Benchmarking Global Analysis

Introduction: Acute Lymphoid Leukemia (ALL) is the leading cause of cancer-related deaths globally among individuals under 20 years of age. Despite its growing burden, there remains a significant gap in high-quality studies analyzing its overall trends. This groundbreaking study provides the first comprehensive examination of the global trends of ALL in the youth over a three-decade period, including the initial two years of the COVID-19 pandemic. During this time, the management of non-COVID-19 conditions, such as ALL, faced unprecedented challenges. Method: Utilizing the Global Burden of Disease Study 2021 meta-tool, we estimated the incidence, prevalence, mortality, and Disability-Adjusted Life Years (DALYs) due to ALL by age, sex, year, and location across 204 countries and territories for individuals under 20 years old from 1990 to 2021. Non-fatal health outcomes were assessed using DISMOD-MR 2.1, a machine learning-based meta-regression tool, while fatal health outcomes were estimated through the Cause of Death Ensemble Model (CODEm). Results: From 1990 to 2021, the Total Percentage of Change (TPC) in the prevalence of ALL rose by 60% (95% Uncertainty Interval: 5-127%), while the number of deaths decreased by 50% (ranging from 31% to 65%). Regionally, the largest increase in TPC prevalence was observed in Andean Latin America at 200%, whereas the largest decrease was noted in Eastern Europe at 38%. In terms of incidence, the most significant rises were recorded in Western Sub-Saharan Africa at 104%, followed by Oceania at 82%, Central Sub-Saharan Africa at 55%, Southern Sub-Saharan Africa at 35%, Eastern Sub-Saharan Africa at 29%, Andean Latin America at 27%, and Australasia at 24%. Conversely, other regions experienced decreases. The highest increase in deaths occurred in Western Sub-Saharan Africa, where they surged by 93% from 1990 to 2021. According to the Socio-Demographic Index (SDI), the highest increase in incidence rates was observed in high-middle SDI countries at 12%. Age-wise, the highest incidence rates in 2021 were found in the 5-9 age group with 12,173 cases, 2-4 years with 10,576 cases, and 10-14 years with 9,342 cases. Regarding mortality, the 5-9 years age group saw 6,710 deaths, followed by 10-14 years at 5,867, 15-19 years at 5,120, 2-4 years at 3,239, less than one year at 1,560, and 12-23 months at 1,494 cases in 2021. Regarding gender, the TPC incidence rates for males decreased by 6%, whereas it decreased by 25% for females. For deaths, the decrease was 45% for males and 57% for females. Similarly, the decline in DALYs was 45% for males and 58% for females from 1990 to 2021. Conclusion: Deaths due to ALL represented 20.95% of all cancer-related fatalities in Individuals Younger Than 20 Years, highlighting its significant impact despite advancements in management strategies. This enduring burden underscores the need for enhanced public health interventions and clinical management. From a public health perspective, there is a critical necessity to strengthen preventive measures, increase awareness, and improve early detection strategies to mitigate the risk factors associated with ALL. Clinically, there is an imperative to refine treatment protocols, personalize therapy based on genetic profiles, and improve supportive care to enhance survival rates and quality of life for affected individuals. Collectively, these efforts will help reduce the prevalence and mortality rates of ALL, ultimately decreasing its overall burden on the healthcare system.