异基因造血干细胞移植患者环孢素A血药浓度监测结果回顾性分析

Retrospective analysis of monitoring results of plasma cyclosporine A concentration in patients with allogeneic hematopoietic stem cell transplantation

【目的】分析异基因造血干细胞移植(allo-geneic hematopoietic stem cell transplantation,Allo-HSCT)患者环孢素(cyclosporine,CsA)血药浓度的影响因素及其对疗效与安全性的影响。【方法】采用荧光偏振免疫分析法测定Allo-HSCT患者CsA血药浓度,收集2012年6月至2018年6月101例Allo-HSCT患者术后的临床资料,回顾性分析患者CsA血药浓度与术后时间、性别、年龄的关系以及其疗效与安全性的关系。【结果】对101例Allo-HSCT患者术后696例次CsA血药浓度结果分析发现,其随术后时间的延长而逐渐降低,不同性别、年龄组的CsA血药浓度也不同,即男性血药浓度比女性的高,儿童组的血药浓度比成人组的低,差异均具有统计学意义(P<0.05)。急性抗宿主病(acute graft-versus-host disease,aGVHD)、肝肾毒性的发生率与术后CsA血药浓度水平具有相关性,CsA血药浓度<200 ng/ml,aGVHD的发生率显著性升高(P<0.05),CsA血药浓度>400 ng/ml,肝肾毒性的发生率显著性升高(P<0.05)。【结论】CsA药动学个体差异大,影响其血药浓度的因素多,其血药浓度的变化可影响疗效和安全性。应根据不同患者的血药浓度,制定个体化给药方案,提高临床疗效与安全性。

【Objective】To analyze the factors affecting the blood concentration of cyclosporine A(CsA)in patients with allogeneic hematopoietic stem cell transplantation,and explore the effect on the efficacy and safety.【Methods】Fluorescence polarization immunoassay(FPIA)was used to determine the plasma concentration of CsA in patients with allogeneic hematopoietic stem cell transplantation.The clinical data of 101 patients with allogeneic hematopoietic stem cell transplantation from June 2012 to June 2018 were collected.The relationship between CsA concentration and postoperative time,gender,age,and its efficacy and safety was analyzed retrospectively.【Results】The results of 696 times of blood concentration determination of CsA in 101 patients with hematopoietic stem cell transplantation showed that its blood concentration decreased gradually with the prolongation of postoperative time.The plasma concentrations of CsA in different gender and age groups were also different at the same time.The male blood concentration was higher than that of the female,and the blood concentration of the children was lower than that of the adults,and the difference was statistically significant.The incidence of aGVHD,liver and kidney toxicity was correlated with the postoperative blood concentration of cyclosporine.When the blood concentration of CsA was less than 200 ng/ml,the incidence of aGVHD significantly increased.When the blood concentration of CsA was more than 400 ng/ml,the incidence of liver and kidney toxicity significantly increased.【Conclusion】The pharmacokinetics of CsA is of great individual difference,and there are many factors affecting the blood concentration of the drug.The changes of blood concentration can affect the efficacy and safety.Individualizing dosage regimens should be developed based on the blood levels of different patients to improve clinical efficacy and safety.