异基因造血干细胞移植患者体内环孢素血药浓度与aGVHD的关系

Relationship between CsA Blood Concentrations and Acute Graft-versus-host Disease after Hematopoietic Stem Cell Transplantation

目的研究异基因造血干细胞移植(allo-HSCT)术后急性移植物抗宿主病(aGVHD)的发生与早期环孢素全血浓度及移植结局的相关性。方法回顾性分析了我院2010年1月至2021年6月期间接受allo-HSCT手术的78例患者的环孢素血药浓度,并评估其临床疗效及不良反应。结果术后第1~4周环孢素中位血药浓度分别为332.7(179.8~602.4)ng·mL^(-1),365.5(95.1~568.4)ng·mL^(-1),366.1(65.9~727.9)ng·mL^(-1),316.8(73.8~727.3)ng·mL^(-1);10名患者在中位时间32天时发生了2~4级aGVHD。在单因素分析中,术后第2、3周浓度较高及HLA配型相合的患者发生2~4级aGVHD的概率显著降低;多因素分析显示,术后第3周环孢素浓度(P=0.042;RR=0.993;95%CI,0.986~1.000)及与干细胞供者HLA配型相合与否(P=0.022;RR=14.19;95%CI,2.21~91.05)是影响2~4级aGVHD的发生率的独立因素;2~4级aGVHD的发生率与移植相关死亡率显著性相关(P=0.022)。结论患者在allo-HSCT术后第2~3周保持较高的环孢素血药浓度能显著降低aGVHD的发生率。而aGVHD的发生与移植术后死亡率相关。

OBJECTIVE To evaluate the relationship between cyclosporine blood concentrations in the early post transplantation period and the incidence of acute graft-versus-host disease and transplant outcomes.METHODS We retrospectively analysed the cyclosporine blood concentrations in the early post transplantation period of 78 patients included from 2010 to 2021.The effectiveness and the safety of cyclosporine were also investigated.RESULTS CsA median blood levels in the 1st,2nd,3rd and 4th weeks after allo-HSCT were 332.7(179.8-602.4)ng·mL^(-1),365.5(95.1-568.4)ng·mL^(-1),366.1(65.9-727.9)ng·mL^(-1),316.8(73.8-727.3)ng·mL^(-1),respectively.10 patients developed grade 2–4 aGVHD at a median of 32 days.In univariate analysis of risk factors for aGVHD(grade 2-4),we found that patients having a higher CsA concentration during the 2nd,3rd week after allo-HSCT and patients receiving allo-HSCT from an HLA-matched donor had a significantly lower risk.In a multivariate logistic regression analysis for aGVHD(grade 2-4),the CsA concentration during the 3rd week after allo-HSCT(P=0.042;RR=0.993;95%CI,0.986-1.000)and patients receiving allo-HSCT from HLA-matched or HLA-mismatched donor(P=0.022;RR=14.19;95%CI,2.21-91.05)were found to be independent factors that were significantly associated with the development of aGVHD(grade 2-4).The incidence of grade 2-4 aGVHD was related to TRM(P=0.022).CONCLUSION We conclude that higher CsA level during the 2nd,3rd week after allo-HSCT and allo-HSCT from HLA-matched donors might predict a lower cumulative incidence of aGVHD after allo-HSCT.The occurrence of aGVHD is related to TRM.