Dosage of 6-Mercaptopurine in Relation to Genetic TPMT and ITPA Variants: Toward Individualized Pediatric Acute Lymphoblastic Leukemia Maintenance Treatment

6-mercaptopurine (6-MP) is the mainstay in pediatric acute lymphoblastic leukemia (ALL) maintenance treatment. Variants in genes coding for thiopurine S-methyl transferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) are known to influence 6-MP metabolism. We determined TPMT and ITPA genotype and enzyme activity and the mean 6-MP doses during maintenance treatment in 40 children treated for ALL according to the Dutch Childhood Oncology Group (DCOG)-ALL11 protocol in the Radboudumc Amalia Children’s Hospital, Nijmegen, The Netherlands. Patients with genetic variants in TPMT (N=3) had significantly lower TPMT enzyme activity (mean 0.46 vs. 0.72 µmol/mmol hemoglobin/h, P=0.005). Although the difference was not statistically significant, they were treated with lower mean 6-MP doses (28.1 mg/m2 [SD 25.5 mg/m2] vs. 41.3 mg/m2 [SD 17.2 mg/m2], P=0.375). In patients with genetic ITPA variants (N=21), ITPA enzyme activity was significantly lowered (mean 3.67 vs. 6.84 mmol/mmol hemoglobin/h, P
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research