缬更昔洛韦抢先治疗异基因造血干细胞移植后巨细胞病毒血症的临床研究  

Valganciclovir for cytomegalovirus preemptive therapy in patients following allogeneic hematopoietic stem cell transplantation

作　　者：陆铉 严晗 夏凌辉[1] LU Xuan;YAN Han;XIA Linghui(Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei Province,430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院血液病研究所,武汉430022

出　　处：《第三军医大学学报》2020年第17期1706-1711,共6页Journal of Third Military Medical University

基　　金：国家自然科学基金青年科学基金(81500109)。

摘　　要：目的比较缬更昔洛韦和常规抗病毒药物(更昔洛韦或膦甲酸钠)在异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation, allo-HSCT)后巨细胞病毒(cytomegalovirus,CMV)血症抢先治疗的疗效,评估缬更昔洛韦在抢先治疗策略中的临床应用价值。方法回顾性分析2017年12月至2019年4月在华中科技大学同济医学院附属协和医院血液病学研究所行allo-HSCT患者139例,按照移植前预处理方案中抗胸腺细胞球蛋白(antithymocyte globulin, ATG)的总剂量,分为无ATG组(n=28)、低剂量ATG(≤6 mg/kg)组(n=73)和高剂量ATG(>6 mg/kg)组(n=38)。采用实时定量聚合酶链反应(real-time quantitative polymerase chain reaction, RQ-PCR)技术检测外周血CMV-DNA水平。对发生CMV血症(CMV-DNA>400拷贝数/mL)的患者,采用缬更昔洛韦或常规抗病毒药物(更昔洛韦或膦甲酸钠)进行抢先治疗。比较不同ATG剂量组的CMV血症发生率和各组治疗后CMV-DNA转阴率、转阴中位时间。结果 allo-HSCT后共有52例患者发生CMV血症,感染率为37.4%(52/139)。无ATG组、低剂量ATG组和高剂量ATG组移植后100 d内CMV感染率分别为14.3%、34.2%、50.0%,差异有统计学意义(P=0.011)。52例发生CMV血症的患者中,使用缬更昔洛韦组(20例)和使用常规抗病毒药物组(32例)患者CMV-DNA转阴率均为100%,但缬更昔洛韦组患者外周血CMV-DNA转阴的中位时间显著少于常规抗病毒药物组(21 d vs 31 d,P=0.022)。高剂量ATG组共有19例患者出现CMV血症,使用缬更昔洛韦组(6例)患者外周血CMV-DNA转阴的中位时间少于常规抗病毒药物组(13例)患者,差异有统计学意义(7 d vs 35 d,P<0.001)。结论 allo-HSCT患者发生CMV血症,使用缬更昔洛韦方案进行抢先治疗可有效缩短CMV-DNA转阴的时间,加速清除外周血中的CMV。在移植期间使用大剂量ATG的患者采用缬更昔洛韦疗效更为显著。Objective To evaluate the clinical value of valganciclovir in preemptive treatment of cytomegalovirus(CMV) infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT) by comparing the efficacy of the drug with other conventional antiviral drugs(ganciclovir or foscarnet sodium). Methods Clinical data of 139 patients who received allo-HSCT in our institute from December 2017 to April 2019 were collected and retrospectively analyzed. According to conditioning regimen and graft versus host disease(GVHD) prophylactic regimen on dosage of antithymocyte globulin(ATG), the patients were divided to ATG-free group(n=28), and low-(≤6 mg/kg, n=73) and high-dose ATG groups(>6 mg/kg, n=38). Real-time quantitative polymerase chain reaction(RQ-PCR) was performed to detect the peripheral blood level of CMV-DNA after transplantation. For the patients having CMV viremia(CMV-DNA >400 copies/mL), valganciclovir and ganciclovir or foscarnet sodium were employed for preemptive treatment. The incidence of CMV viremia, and clearance rate and median time of plasma CMV-DNA were compared among the different dose ATG group and conventional drug group. Results CMV viremia was observed in 52 patients, with an incidence of 37.4%(52/139). Within 100 d after transplantation, the incidence of CMV viremia was 14.3%, 34.2% and 50.0%, respectively, in the ATG-free group, low-and high-dose ATG groups(P=0.011). Among these 52 patients, the clearance rate of plasmic CMV-DNA was 100% in both valganciclovir group(n=20) and conventional antiviral group(n=32). However, the median time of CMV-DNA clearance was significantly shorter in the valganciclovir group than the conventional antiviral group(21 vs 31 d, P=0.022). In the high-dose ATG group, the median time of clearance of plasma CMV-DNA was significantly shorter in the valganciclovir group(6 cases) than the conventional antiviral group(13 cases)(7 vs 35 d, P<0.001). Conclusion Preemptive treatment with valganciclovir can effectively shorten the time and accelerate the clearance of pl

关 键 词：巨细胞病毒血症 异基因造血干细胞移植 缬更昔洛韦 抢先治疗 抗胸腺细胞球蛋白 

分 类 号：R512.99[医药卫生—内科学] R617[医药卫生—临床医学]