Study to determine the thiopurine methyltransferase (TPMT) status in children with acute lymphoblastic leukemia to customize thiopurine dosage.

e21005 Background: Daily mercaptopurine constitutes one of the standard “backbone” of Acute Lymphoblastic leukemia continuation regimens. Tailoring the dosages of methotrexate and mercaptopurine to the limits of tolerance has been associated with a better outcome. We determined the TPMT genotype in children with acute lymphoblastic leukemia before commencing thiopurine therapy to customize the dosage of mercaptopurine. Methods: This is a single institution prospective study of 32 children from 0 to 18 years newly diagnosed as acute lymphoblastic leukemia by flow cytometry from January 2014 to December 2015. The TPMT genotype status of the child was detected by peripheral blood TPMT Genotyping PCR (Qualitative) and RFLP Analysis. The analysis was done for five genotypes TPMT* 1 Wild Type, TPMT* 2, TPMT* 3A, TPMT* 3B and TPMT* 3C. The prevalence of TPMT polymorphisms were correlated with the hematological toxicities. Results: A total of 32 samples were analysed for TPMT genotype status. The male:female ratio was 2.2:1. 26 (81%) of them were diagnosed as B cell ALL. All the 32 were found to have TPMT* 1 Wild Type genotype consistent with normal enzyme activity. The average tolerated dose of 6-mercaptopurine during consolidation phase was 36 mg/m2/day as against the recommended dose of 60 mg/m2/day. The average dose of 6-mercaptopurine tolerated during the maintenance phase was 27 mg/m2/day as against the recommended dose of 75 mg/m2/day. Conclusions: The absence of TPMT mutations did not seem to account for the reduced tolerance of 6-mercaptopurine in our population. However studies with larger sample size in our population is required to ascertain this. This opens up further studies of variant genes other than TPMT involved in transformation of 6-mercaptopurine and polymorphisms in genes of folate metabolism to be evaluated in the Indian population.