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

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(−1) vs 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) vs 4.61 ng·ml(−1)·mg(−1), 5.65 ng·ml(−1)·mg(−1) vs 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.