Farmakogenetiska testers användning och kliniska betydelse vid behandling av pediatriska hematologiska patienter vid Åbo universitetscentralsjukhus

Interindividual genetic variability in the activity of thiopurine methyl transferase (TPMT) and nudix hydrolase 15 (NUDT15) enzymes affect the metabolism of mercaptopurine, a cornerstone drug in the treatment of acute lymphoblastic leukaemia (ALL). Reduced or completely deficient enzyme activity is associated with decreased elimination of mercaptopurine, leading to systemic overexposure and dose-dependent toxicity, thereby increasing the risk of treatment failure or disease relapse. Therefore, pharmacogenetic testing is used to guide the appropriate mercaptopurine dose. This retrospective cohort study included patients treated in the Paediatric and Adolescent Haematology and Oncology Department at the Turku University Hospital (TYKS) between 2019 and 2024 who had undergone a pharmacogenetic test. The primary objective was to investigate the impact of test results on drug treatment in two ways: (1) to assess whether test results were considered in the cancer treatments, and (2) to identify other medications for which the pharmacogenetic test results may have clinical relevance. A total of 40 patients with pharmacogenetic test data were included, with panel testing performed in 24 patients and TMPT testing in 16 patients. Three patients (7.5%) were classified as TPMT intermediate metabolisers (IM), and in all cases protocol-specific recommendations were followed with dose reductions. All NUDT15-tested patients (n=24) were classified as normal metabolisers (NM). Ten of the 24 panel-tested patients (42%) had at least one actionable gene–drug pair among the other pharmacogenetically actionable drugs. This study showed that protocol-specific dose reductions were implemented for patients classified as intermediate metabolisers (IM) or poor metabolisers (PM) of TPMT and/or NUDT15. Moreover, other prescribed drugs with pharmacogenetic recommendations were commonly used, with up to 42% of patients had at least one actionable gene–drug pair. These findings suggest that pharmacogenetic test results should be considered across a patient’s entire medication regimen, which may be challenging for healthcare professionals.