[The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation].

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(-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.

• Authors: X Chen, R L Zhang, W H Zhai, Q L Ma, A M Pang, D L Yang, Y He, J L Wei, E L Jiang, S Z Feng, M Z Han
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 42 Issue 10 Pg. 828-833 (Oct 14 2021) ISSN: 0253-2727 [Print] China
• PMID: 34788922 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• CYP3A5 protein, human
• Cytochrome P-450 CYP3A
• Tacrolimus

Topics

• Cytochrome P-450 CYP3A (genetics)
• Graft vs Host Disease (prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Immunosuppressive Agents
• Polymorphism, Genetic
• Retrospective Studies
• Tacrolimus