Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia?
Author(s): Fakhoury M, Andreu-Gallien J, Mahr A, Medard Y, Azougagh S, Vilmer E, Jacqz-Aigrain E Affiliation(s): Paediatric Pharmacology and Pharmacogenetic Department, Robert Debre Hospital, Paris, France. Publication date & source: 2007-12, J Clin Pharm Ther., 32(6):633-9. Publication type: BACKGROUND AND OBJECTIVE: The activity of thiopurine S-methyltransferase (TPMT), a key enzyme in the metabolism of purine analogues, displays wide inter-subject variability partly due to a genetic polymorphism. Previous studies have suggested adjusting purine analogues dosing according to TPMT activity but measurements are costly and time-consuming. It is still unclear, especially under treatment, whether the simpler TPMT genotyping reliably predicts enzyme activity. Our aim was to study the possible correlation of TPMT genotype with phenotype. METHODS: We determined the genotypic status and TMPT activity, at diagnosis and after 6 months of maintenance therapy, of 118 children with acute lymphobla