Objective: To investigate herpesvirus infection in early stage of hematopoietic stem cell transplantation (HSCT) by multiplex polymerase chain reaction (PCR), and to explore the association between multiple herpesviruses infection and clinical characteristics in HSCT patients and its impact on post-transplant complications and prognosis. Methods: A total of 734 peripheral blood samples were collected from 90 patients undergoing HSCT in the Department of Hematology, the First Affiliated Hospital of Soochow University between February 2017 and August 2017. The peripheral blood specimens were obtained before and within 90 days after transplantation at different time points. Lab-Aid824 Nucleic Acid Extraction Mini Reagent was used to extract DNA and multiplex PCR assay was used to simultaneously detect 8 kinds of human herpesviruses from genomic DNA. The incidence of various herpesvirus infections, its correlation with clinical features and effects on post-transplant complications and prognosis were analyzed. Results: The median follow-up time was 192 (range: 35-308) days. Among the 90 patients before transplantation, the incidence of herpes virus infection was 35.6% (32/90), including 12.2% (11/90) with one herpes virus infection and 23.3% (21/90) with multiple viruses infection. The incidence of herpes virus infection after transplantation was 77.8% (70/90), including 20.0% (18/90) with one herpes virus infection and 57.8% (52/90) with multiple herpes virus infection. Among the 52 patients with multiple herpes viruses infection, 30 (57.7%) patients were infected by 2 kinds of viruses, 18 (34.6%) patients by 3 kinds of viruses and 4 (7.7%) patients by 4 kinds of viruses. There was a correlation between HHV-6 and HHV-7 herpesvirus infection (OR=13.880, Q=0.026). EBV infection was related to HHV-7 infection (OR=0.093, Q=0.044). The age of patients was correlated with the incidence of HHV-1 infection before transplantation. There were 24 patients in our study experienced clinical symptoms associated with viral infection. The main manifestations were hemorrhagic cystitis (HC), interstitial pneumonia, enteritis, viral encephalitis and fever of unknown origin. EBV infection was related to HLA incompatibility and the inconsistent of the ABO blood group and grade Ⅱ-Ⅳ aGVHD after transplantation. HLA incompatibility and the unrelated donor and grade Ⅱ-Ⅳ aGVHD were related to multiple viruses infection. Conclusion: Multiple herpesviruses were common in patients undergoing HSCT, which were closely related to HLA mismatch, unrelated donor and grade Ⅱ-Ⅳ aGVHD.
目的： 采用多重PCR方法分析造血干细胞移植（HSCT）患者多种疱疹病毒的感染状况，并探讨HSCT患者多种疱疹病毒感染与临床特征的相关性及其对移植并发症和预后的影响。 方法： 以苏州大学附属第一医院血液科2017年2月至2017年8月行HSCT的90例患者为研究对象，收集预处理至移植后90 d内不同时间点的外周血标本共734份，Lab-Aid824核酸提取Mini试剂抽提DNA，应用多重PCR方法同时扩增8种人类疱疹病毒，分析多种疱疹病毒感染发生率及其与临床特征的相关性及对移植后并发症和预后的影响。 结果： 至随访终点，中位随访时间为192（35~308）d。移植前疱疹病毒感染发生率为35.6%（32/90），其中1种疱疹病毒感染发生率为12.2%（11/90），多种病毒感染的发生率为23.3%（21/90）。移植后疱疹病毒感染发生率为77.8%（70/90），其中1种疱疹病毒感染发生率为20.0%（18/90），多种疱疹病毒感染的发生率为57.8%（52/90）。在多种疱疹病毒感染的患者中，2种病毒感染30例（57.7%），3种疱疹病毒感染18例（34.6%），不同时间点样本检测的4种疱疹病毒感染4例（7.7%）。移植后多种疱疹病毒感染中，HHV-6和HHV-7感染存在相关性（OR=13.880，Q=0.026），EBV和HHV-7感染也存在相关性（OR=0.093，Q=0.044）。25例患者移植后出现疱疹病毒感染相关临床表现，主要为出血性膀胱炎、间质性肺炎、肠炎、病毒性脑炎和不明原因发热。移植前HHV-1感染与年龄、HHV-2感染与发病时间、CMV感染与原发病为淋巴瘤具有一定的相关性。移植后EBV感染与HLA不全相合、供受者ABO血型不一致及Ⅱ~Ⅳ度急性GVHD呈正相关；多种疱疹病毒感染与HLA不全相合、非血缘供者及Ⅱ~Ⅳ度急性GVHD呈正相关。 结论： HSCT前后存在多种疱疹病毒感染，HLA不全相合、非血缘供者和Ⅱ~Ⅳ度急性GVHD与移植后多种疱疹病毒感染存在一定的相关性。.
Keywords: Hematopoietic stem cell transplantion; Multiple herpesviruses; Multiplex PCR assay.