实时定量聚合酶链反应检测巨细胞病毒在同种异基因造血干细胞移植术后监测中的意义  

Clinical significance of real-time quantitative PCR analysis of cytomegalovirus in patients receiving allogeneic hematopoietic stem cell transplantation

作　　者：王苓[1] 唐暐[1] 赵维莅[1] 陈玉宝[1] 沈志祥[1] 季育华[2] 胡炯[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院血液科造血干细胞移植中心,上海200025 [2]上海交通大学医学院附属瑞金医院检验科,上海200025

出　　处：《诊断学理论与实践》2010年第1期19-24,共6页Journal of Diagnostics Concepts & Practice

摘　　要：目的:探讨同种异基因造血干细胞移植(allo-HSCT)中巨细胞病毒(cytomegalovirus,CMV)激活情况及激活相关因素。方法:52例接受allo-HSCT的患者为研究对象,所有患者及其供者移植前均为CMV携带者,即为CMV血清型阳性。所有移植术后患者应用实时定量聚合酶链反应(PCR)方法对CMVDNA进行定量检测。结果:移植后100d内,52例患者中28例检测到CMVDNA复制。造血干细胞移植(HSCT)供者类型和移植物抗宿主反应(graft versus host disease,GVHD)的发生与CMV激活明显相关(P值分别为0.018和0.039)。在44例可评估患者中,allo-HSCT100d后仅7例检测到CMVDNA复制,其发生率与移植后发生GVHD且接受激素治疗(P=0.0009)、人类白细胞抗原(HLA)全相合无关供者移植或者HLA部分相合同胞供者移植有关(P=0.037)。应用实时定量PCR检测发现,CMV对更昔洛韦抢先治疗的应答存在2种动力学模式(快速型和缓慢型),其中表现为缓慢型的患者CMV最高负载量较快速型高10倍以上,其病毒衰减时间也要延长3～4周,多数发生在因出现GVHD而接受激素治疗以及接受HLA全相合无关供者和HLA部分相合同胞供者干细胞移植的患者。结论:移植前CMV血清型阳性患者接受allo-HSCT后100d内出现CMV激活是常见并发症。移植100d之后,对于未发生GVHD而未使用激素治疗者或以HLA全相合同胞为供体的患者,CMV激活概率低,无需进行常规频繁监测。Objective Cytomegalovirus （CMV） reactivation is a high risk for CMV disease and remains as an important complication for patients receiving allogeneic hematopoietic stem cell transplantation （allo-HSCT）.Methods Fifty-two consecutive patients receiving allo-HSCT were enrolled.All the patients and donors were CMV seropositive.Quantification of CMV DNA was performed by real-time polymerase chain reaction （PCR）.Results Within the course of 100 days after transplantation,positive CMV DNA was detected in 28 of the 52 patients.The donor type and occurrence of graft versus host disease （GVHD） correlated with the incidence of CMV reactivation （P=0.018 and P= 0.039,respectively）.After 100 days,for the 44 evaluable patients with follow-up longer than 100 days,positive CMV DNA was detected in only 7 patients.The incidence was correlated with steroid treatment for GVHD （P=0.0 009）,and transplantation with HLAmatched unrelated donors or partially mismatched related donor （P=0.037）.Two types of kinetic models to preemptive ganciclovir therapy were observed.The ‘slow response＇ type was associated with a 10 fold higher peak CMV viral load than the ‘rapid response＇ type,and the duration of positive CMV DNAemia in ‘slow response＇ type was 3-4 weeks longer than that in ‘rapid response＇ type.The ‘slow response＇ type was observed more likely in patients with steroid treatment for GVHD,with transplants from HLA-matched unrelated donor or partially mismatched related donor.Conclusions CMV reactivation is frequent in CMV seropositive patients receiving allo-HSCT from CMV seropositive donors within 100 days.After 100 days,patients with no GVHD and steroid treatment,receiving transplants from HLA matched related donor had low incidence of CMV reactivation,routine close monitoring is not necessary for these patients.

关 键 词：同种异体造血干细胞移植 巨细胞病毒 实时定量聚合酶链反应 

分 类 号：R519[医药卫生—内科学]