The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation
10.3760/cma.j.issn.0253-2727.2021.10.006
- VernacularTitle:CYP3A5基因多态性对异基因造血干细胞移植患者他克莫司血药浓度和不良事件的影响
- Author:
Xin CHEN
1
;
Rongli ZHANG
;
Weihua ZHAI
;
Qiaoling MA
;
Aiming PANG
;
Donglin YANG
;
Yi HE
;
Jialin WEI
;
Erlie JIANG
;
Sizhou FENG
;
Mingzhe HAN
Author Information
1. 中国医学科学院血液病医院（中国医学科学院血液学研究所），实验血液学国家重点实验室，国家血液系统疾病临床医学研究中心，天津 300020
- Keywords:
CYP3A5 genotype;
Tacrolimus;
Blood drug concentration;
Hematopoietic stem cell transplantation
- From:
Chinese Journal of Hematology
2021;42(10):828-833
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigates the relationship between CYP3A5 gene polymorphism, tacrolimus concentration, and acute graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical data of 35 Chinese adult patients who received allo-HSCT from July 2019 to February 2020 was conducted. Also, bone marrow samples were collected before transplantation for CYP3A5 genotyping, and intravenous infusion of tacrolimus and a short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15 ng/ml) .Results:In 16 allo-HSCT patients with CYP3A5 *3/*3 gene, the initial concentration of tacrolimus (9.82 ng/ml vs 8.53 ng/ml) , the initial concentration/dose (C/D) ratio (5.72 ng·ml -1·mg -1vs 4.26 ng·ml -1·mg -1) , and the median C/D ratio in the first two weeks after HSCT (5.29 ng·ml -1·mg -1vs 4.61 ng·ml -1·mg -1, 5.65 ng·ml -1·mg -1vs 4.56 ng·ml -1·mg -1) were significantly higher than in 19 patients with at least one CYP3A5 * 1 allele ( P=0.028, 0.001, 0.037, 0.045) . The incidence of Ⅲ-Ⅳ aGVHD in patients with CYP3A5*1 alleles was higher than in patients with CYP3A5*3/*3 gene[ (26.3±10.1) % vs (6.2±6.1) %, P=0.187]. Conclusion:CYP3A5 genotype-directed administration may help achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD, and improve the efficacy of transplantation.
