Should TPMT genotype and activity be used to monitor 6-mercaptopurine treatment in children with acute lymphoblastic leukaemia?

Summary 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 lymphoblastic leukaemia (ALL). Results and Discussion: Eighty‐nine per cent of the children had a homozygous wild‐type genotype (group 1), 11% had one or two mutant allele(s) (group 2). At both time points, TPMT activity (U/mL peripheral red blood cell) was significantly higher in group 1 than in group 2 (P