摘要
Abstract
Background 6-mercaptopurine(6-MP)is one of the main drugs used in the maintenance therapy of acute lymphoblastic leukemia(ALL),and its metabolism enzyme gene polymorphism is associated with the degree of bone marrow suppression caused by the drug.Objective To investigate the relationship between the dose of 6-MP use and TPMT and NUDT15 gene polymorphisms during maintenance therapy in children with ALL.Design Retrospective cohort study.Methods Children with a clear diagnosis of ALL at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were included,who achieved complete remission after prior chemotherapy and entered the maintenance therapy stage with oral 6-mercaptopurine(6-MP)treatment.Before starting oral 6-MP,genetic testing for TPMT and NUDT15 genotypes was conducted to analyze the dosage and bone marrow suppression of 6-MP treatment in children with different TPMT and NUDT15 genotypes.Main outcome measures 6-MP dosage.Results This study analyzed 61 pediatric ALL patients undergoing maintenance therapy.Among them,48 patients were included in the statistical analysis of TPMT gene polymorphism(excluding 13 cases with NUDT15 gene mutations),with 45 wild-type cases and 3 mutant cases.Additionally,58 patients were included in the statistical analysis of NUDT15 gene polymorphism(excluding 3 cases with TPMT gene mutations),with 45 CC genotype cases,9 CT genotype cases,and 4 TT genotype cases.During the maintenance therapy with 6-MP,significant differences in WBC,Hb,and PLT counts were observed among patients with different TPMT and NUDT15 genotypes(all P＜0.05).Patients experienced varying degrees of neutropenia after medication,including 15 cases with wild-type TPMT and 3 mutant TPMT cases,as well as 15 CC genotype cases,5 CT genotype cases,and 4 TT genotype cases of NUDT15 gene.The differences in bone marrow suppression among patients with different TPMT and NUDT15 genotypes were statistically significant(all P＜0.05).Furthermore,there were significant differences in the dosage of 6-MP among patients with different TPMT and NUDT15 genotypes(all P＜0.05).Specifically,the maintenance therapy dosage of 6-MP for patients with wild-type TPMT and mutant TPMT was(40.81±6.02)and(16.25±4.42)mg·m-2·d-1,respectively.For patients with CC genotype,CT genotype,and TT genotype of the NUDT15 gene,the 6-MP dosage was(40.81±6.02),(34.28±4.53),and(10.00±1.28)mg·m-2·d-1,respectively.Conclusion Patients with mutations in the TPMT and NUDT15 genes experience more severe bone marrow suppression compared to those with the wild-type genotype.The dosage of 6-MP used during maintenance therapy in pediatric ALL patients is associated with TPMT and NUDT15 gene polymorphisms.关键词
急性淋巴细胞白血病/6-巯基嘌呤/TPMT/NUDT15/基因多态性/药物使用剂量Key words
Acute lymphoblastic leukemia/6-mercaptopurine/TPMT gene/NUDT15 gene/Genetic polymorphism/Dosage of drugs
