Health Technology Assessment of Thiopurine Methyltransferase Testing for Guiding 6-mercaptopurine Doses in Paediatric Patients with Acute Lymphoblastic Leukemia

Produced by Technology Assessment at SickKids, Hospital for Sick Children.During the final maintenance phase of therapy for childhood leukemia, an immunosuppressive agent called 6-mercaptopurine (6-MP) is used. The risks of certain adverse drug events (ADE) as a result of 6-MP-treatment are influenced by genetic variations within the population in the enzyme responsible for metabolizing 6-MP, thiopurine methyltransferase (TPMT). There are currently two methods of detecting TPMT enzyme deficiency: a phenotype test (enzymatic assay) that gives a metabolite activity reading and a genotype test that detects the presence of mutations in the genes responsible for producing the TPMT enzyme. Given the high cost of genetic testing and the importance of preventing ADEs, understanding the incremental cost-effectiveness of either form of testing compared to standard care (no testing) would be valuable to guide therapy. The primary objective was to review the literature systematically to determine the accuracy of TPMT phenotype and and genotype tests. The secondary objective was to determine the incremental cost of TPMT genotyping and phenotyping compared to standard weight-based dosing strategies per life-month saved.Supported by the Atlantic Canada Opportunities Agency, the Government of Newfoundland and Labrador, Memorial University of Newfoundland, the Ontario Ministry of Health and Long-Term Care Drug Innovation Fund, and the Newfoundland and Labrador Centre for Health Information