Hyperlipidemia in children and adolescents with acute lymphoblastic leukemia: A systematic review and meta-analysis

Background: The established association between acute lymphoblastic leukemia (ALL) and hyperlipidemia has, in some studies, been linked to toxicities such as pancreatitis, thrombosis, and osteonecrosis. However, a systematic review investigating the incidence, management, and clinical implications of hyperlipidemia during childhood ALL treatment is lacking.Objectives: Systematically assess the incidence of hyperlipidemia during ALL treatment, explore associations with risk factors and severe toxicities (osteonecrosis, thrombosis, and pancreatitis), and review prevalent management strategies.Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Data synthesis was descriptive, and a meta-analysis of hypertriglyceridemia and risk of severe toxicities was performed.Results: We included 13 studies with 3,425 patients. Hyperlipidemia incidence varied widely (6.7%-85%) but with inconsistent definitions and screening strategies across studies. Evidence regarding risk factors was conflicting, but age (> 10 years) and treatment with asparaginase and glucocorticosteroids seem to be associated with hyperlipidemia. Hypertriglyceridemia (grade 3/4) increased the risk for osteonecrosis (odds ratio (OR): 4.27, 95% confidence interval (CI): 2.77-6.61). No association could be established for pancreatitis (OR: 1.60, 95% CI: 0.53-4.82) or thrombosis (OR: 2.45, 95% CI: 0.86-7.01), but larger studies are needed to confirm this.Conclusion: The overall evidence of this systematic review is limited by the small number of studies and risk of bias. Our review suggests that hypertriglyceridemia increases the risk for osteonecrosis. However, larger studies are needed to explore the clinical implications of hyperlipidemia and randomized trials investigating hyperlipidemia management and its impact on severe toxicities.