Pharmacogenetic profiling of paediatric oncology patients: a single-centre experience

Aim: As the results of pharmacogenetic studies are increasingly translated into clinical practice, the ultimate goal of personalising treatment for children with cancer seems achievable in the future. Our survey aimed to establish to what extent pharmacogenetics has already been utilised in everyday work. Methods: A retrospective survey on pharmacogenetic testing in children treated for malignancies at the Department of Oncology and Haematology, Children’s Hospital Zagreb, from 2021 to 2023 was carried out. Results: Pharmacogenetic testing was performed in 17.2% of the 180 children (53.3% female, median age 7.0 years), the greatest number of tests obtained in 2023. Preemptive testing included thiopurine S-methyltransferase polymorphisms (in 94.4% of children with acute lymphoblastic leukaemia and 33.3% with eosinophilic granuloma) and methylenetetrahydrofolate reductase gene poly- morphisms assaying (in 55.6% of acute lymphoblastic leukaemia and 23.1% of osteosarcoma patients). In 8 children, pharmacoge- netic testing was made due to adverse events (25% lung and 75% liver injury, all grade 4), in the majority of cases presumably related to vincristine. Pharmacogenetic testing results were pathological in all reactively tested patients, requiring dose modification/che- motherapeutics omission in 87.5% of cases. Conclusion: The number of pharmacogenetic assays performed due to high-grade adverse events in children with cancer has been continuously rising, steering otherwise standardised treatment towards a more individualised approach. Preemptive thiopurine Methyltransferase Polymorphism testing has been routinely done in almost all patients planned to receive thiopurines. However, more research is needed on drug-gene pairs in the field of paediatric oncology to minimise treatment-related toxicity and optimise treatment outcomes.

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