genetic variants are related to thiopurine-induced neutropenia in Thai children with acute lymphoblastic leukemia.

: 6-Mercaptopurine (6MP) is key to the treatment of acute lymphoblastic leukemia (ALL) as part of maintenance therapy. was identified as a novel thiopurine regulator conferring 6MP sensitivity. The aim of this study was to evaluate the influence of variants on 6MP-induced neutropenia in Thai children with ALL. : Genotyping of (c.415C>T; rs116855232) and c.36_37insGGAGTC; rs554405994) was performed by Sanger sequencing in 100 patients with ALL. Patients were classified into wild-type (group 1), heterozygous variant (group 2) and homozygous variant (group 3). Clinical and laboratory features during the first 6 months of maintenance therapy were investigated. Therapy-induced neutropenia was observed in 31 patients during the weeks 1-8 (early myelotoxicity), while therapy-induced neutropenia was observed in 47 patients during the weeks 9-24 (late myelotoxicity). : There were 85 wild-type patients, 14 heterozygous variant patients and one homozygous variant patient. variants were associated with neutropenia as compared with wild-type (odds ratio: 17.862; 95% CI: 4.198-75.992, p = 9.5 × 10). Multivariate analysis showed that the low-risk group was associated with neutropenia (p = 0.014) in the first 8 weeks of 6MP therapy. Group 2 and group 3 patients had significantly lower absolute neutrophil counts compared with group 1. The adjusted dose during the first 6 months of maintenance therapy with genotype group 1, 2 and 3 were 50, 36.6 and 12.5 mg/m/day, respectively. : Taken together, our results indicate variants may cause neutropenia, and the 6MP dosage should be considered in patients according to the variants to inform personalized 6MP therapy.