Genetic polymorphisms associated with L-asparaginase–related toxicity in children with acute lymphoblastic leukaemia: A systematic review protocol (2020–2026)

This registration outlines the protocol for a systematic review investigating genetic polymorphisms associated with L-asparaginase-related toxicities in children with acute lymphoblastic leukaemia (ALL). L-asparaginase is a critical component of paediatric ALL treatment; however, its use is frequently complicated by clinically significant toxicities, including hepatotoxicity, acute pancreatitis, thrombosis, hypersensitivity reactions, and metabolic disturbances. Interindividual variability in the development and severity of these adverse events suggests a genetic contribution. The objective of this review is to systematically identify and synthesise contemporary evidence (2020–2026) on single nucleotide polymorphisms (SNPs) associated with L-asparaginase-related toxicity in paediatric ALL patients. The findings will inform the development of candidate genetic panels for toxicity risk stratification and support personalised therapeutic approaches. The review will follow PRISMA-P guidelines. Eligible studies will include observational and pharmacogenomic association studies conducted in paediatric populations. Data will be extracted on study characteristics, genetic variants investigated, toxicity outcomes, and effect estimates. Risk of bias will be assessed using the Newcastle–Ottawa Scale adapted for genetic association studies. Where appropriate, meta-analysis will be performed; otherwise, findings will be synthesised narratively. The results are expected to provide a structured foundation for future translational pharmacogenomic research and clinical implementation strategies.