[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及不良事件的影响]
[The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation].
作者信息
Chen X, Zhang R L, Zhai W H, Ma Q L, Pang A M, Yang D L, He Y, Wei J L, Jiang E L, Feng S Z, Han M Z
机构信息
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2021 Oct 14;42(10):828-833. doi: 10.3760/cma.j.issn.0253-2727.2021.10.006.
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) . 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) . In 16 allo-HSCT patients with CYP3A5 3/3 gene, the initial concentration of tacrolimus (9.82 ng/ml 8.53 ng/ml) , the initial concentration/dose (C/D) ratio (5.72 ng·ml(-1)·mg(-1) 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(-1) 4.61 ng·ml(-1)·mg(-1), 5.65 ng·ml(-1)·mg(-1) 4.56 ng·ml(-1)·mg(-1)) were significantly higher than in 19 patients with at least one CYP3A5 * 1 allele (=0.028, 0.001, 0.037, 0.045) . The incidence of Ⅲ-Ⅳ aGVHD in patients with CYP3A51 alleles was higher than in patients with CYP3A53/*3 gene[ (26.3±10.1) % (6.2±6.1) %, =0.187]. 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.
探讨异基因造血干细胞移植（allo-HSCT）患者中CYP3A5基因多态性、他克莫司浓度与急性移植物抗宿主病（GVHD）之间的关系。对2019年7月至2020年2月接受allo-HSCT的35例中国成年患者的临床资料进行回顾性分析。此外，在移植前采集骨髓样本进行CYP3A5基因分型，并采用静脉输注他克莫司和短疗程甲氨蝶呤（MTX）±霉酚酸酯预防GVHD。在他克莫司给药的第二天或第三天监测初始浓度，随后每周监测2 - 3次。根据目标血药浓度（10 - 15 ng/ml）调整药物剂量。在16例CYP3A5 *3/*3基因的allo-HSCT患者中，他克莫司的初始浓度（9.82 ng/ml±8.53 ng/ml）、初始浓度/剂量（C/D）比值（5.72 ng·ml⁻¹·mg⁻¹±4.26 ng·ml⁻¹·mg⁻¹）以及HSCT后前两周的中位C/D比值（5.29 ng·ml⁻¹·mg⁻¹±4.61 ng·ml⁻¹·mg⁻¹，5.65 ng·ml⁻¹·mg⁻¹±4.56 ng·ml⁻¹·mg⁻¹）均显著高于19例至少有一个CYP3A5 *1等位基因的患者（P = 0.028，0.001，0.037，0.045）。CYP3A5 *1等位基因患者的Ⅲ-Ⅳ级急性GVHD发生率高于CYP3A5 *3/*3基因患者[（26.3±10.1）%比（6.2±6.1）%，P = 0.187]。CYP3A5基因型指导给药可能有助于更快达到HSCT后他克莫司的目标血药浓度，降低严重急性GVHD的发生率，并提高移植疗效。
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