异基因造血干细胞移植术后巨细胞病毒感染与慢性移植物抗宿主病的关系

Study of the Relationship between the Cytomegalovirus Infection and Chronic Graft Versus Host Disease in Patients with Leukemia after Allogeneic Haemotopoietic Stem Cell Transplantation

目的探讨白血病患者异基因造血干细胞移植(Allo-HSCT)术后巨细胞病毒(CMV)感染与慢性移植物抗宿主病(cGvHD)的关系。方法以56例自体干细胞移植(Auto-HSCT)患者为对照,对92例Allo-HSCT患者在术后100～360d内采用单克隆抗体免疫荧光测定法、微粒子酶免分析法分别每月检测1次外周血中CMV-Ag阳性细胞数和CMV-IgM滴度,对其中30例cGvHD患者还同时采用酶联免疫吸附法检测其外周血中肿瘤坏死因子α(TNFα)和白细胞介素2(IL)2的水平。结果Allo-HSCT术后100d～1a内,CMV活动性感染发生率(65.2%)高于Auto-HSCT组(10.7%),差别有统计学意义(P<0.05);Allo-HSCT后,CMV活动性感染的患者发生cGvHD的风险是静止性感染患者的6.75倍。有cGvHD患者中,CMV活动性感染期广泛性cGvHD发生的相对风险为静止性感染期的5.5倍,且患者外周血中TNFα([481±19.6)ng/L]和IL2([214±16.7)ng/L]高于此期局限性cGvHD患者([239±17.2)ng/L]和([103±15.5)ng/L],也高于静止期广泛性cGvHD患者([236±12.8)ng/L]和([79.1±9.5)ng/L]。结论在Allo-HSCT术后,CMV活动性感染可通过增加外周血中TNFα和IL2的水平来增加cGvHD的发生率和严重程度。

Objective To investigate the relationship between the cytomegalovirus （CMV） infection and chronic graft versus host disease （cGvHD） in patients with leukemia after allogeneic haemotopoietic stem cell transplantation（Allo-HSCT）. Methods 56 cases with auto-HSCT were used as control group, CMV-Ag positive cells and CMV-IgM titers of 92 cases with allo-HSCT were detected once a month from the 100th to 360th days after transplantation by monoclone antibody immunofluorescence assay and microparticle enzyme immunoassay respectively. To 30 patients with cGvHD of them, the levels of TNFα and IL2 in peripheral blood were also detected by euzymelinked immanosorbent assay. Results The incidence of CMV active infection during this period for Allo-HSCT and Auto-HSCT was 65.2% and 10.7% respectively, and the difference between them was statistical significance （P〈0.05）. The risk of cGvHD in patients with CMV active infection was 6.75 times higher than that in patients with CMV stationary infection. During the active period of CMV infection, the relative risk of extensive cGvHD was 5.5 times higher than that in the stationary phase. Moreover, the average levels of TNFα（481 ±19.6 ng/L）and IL2 （214± 16.7 ng/L）in these patients were higher than those in patients with limited cGvHD （239±17.2 ng/L and 103±15.5 ng/L） and also much higher than extensive cGvHD patients in the stationary phase （236±12.8 ng/L and 79.1 ±9.5 ng/L）. Conclusion In patients with AIIo-HSCT, CMV active infection can increase the incidence and severity of cGvHD by elevating the levels of TNFα and IL2 in peripheral blood.