BK病毒在干细胞移植术后出血性膀胱炎中的作用研究

The role of BK polyomavirus in the development of hemorrhagic cystitis after hematopoietic stem cell transplantation

目的探讨BK病毒在造血干细胞移植术（HSCT）后出血性膀胱炎（HC）中的致病作用，分析BK病毒尿及HC的相关危险因素。方法收集2006年8月至2007年11月间80例HSCT患者的血、尿标本，用PCR方法检测BK病毒DNA，同时用免疫荧光组化法检测血巨细胞病毒（CMV）抗原，20例健康成人为正常对照。结果80例HSCT患者中15例发生HC（发病率18．8％），中位发生时间为移植后44（13—150）d，持续时间11（2—25）d。80例患者中尿检出BK病毒30例（检出率37．5％），其中13例为HC患者（占HC组86．7％）。HC患者尿BK病毒中位检出时间为移植后23（0—56）d，早于HC发生时间。尿BK病毒持续阳性中位时间为7（2—14）周，长于HC持续时间。80例HSCT患者中12例检出CMV抗原血症，尿BK病毒阳性组检出率为36．7％（11／30），HC患者检出率为40．0％（6／15）。30例尿BK病毒阳性患者中9例发生Ⅱ-Ⅳ度急性移植物抗宿主病（aGVHD）（30．0％）。有2例HC患者及20例正常对照者未检出BK病毒尿。所有血标本BK病毒检测均阴性。单因素分析显示CMV抗原血症、Ⅱ-Ⅳ度aGVHD是BK病毒尿的危险因素。结论BK病毒尿是HSCT术后迟发性HC的主要发病原因，CMV感染与aGVHD可能诱发BK病毒相关性HC的发生。

Objective To study the role of BK virus （ BK polyomavirus） in the development of the hemorrhagic cystitis （HC） after hematopoietic stem cell transplantation （HSCT） and analyze the risk fators for BK viruria and HC. Methods From August 2006 to November 2007, blood and urine samples were collected from 80 patients undergoing HSCT. BK virus DNA was detected with PCR. Cytomegalovirus （CMV） antigen was detected with immunofluorescence histochemical examination. A control group including 20 healthy individuals was established. Results Late-onset HC occurred in 15 of the 80 HSCT patients with an incidence of 18.8%. The median onset time of HC was 44（13-150） days after transplantation. BK viruria was detected in 30 of the 80 HSCT patients （37. 5% ） and the positive rate of viruria in the HC patients was 86.7% （13/15）. The median time of BK viruria detection in HC patients was 23 （0-56） days after transplantation, being earlier than the onset time of HC. The persistence time of BK viruria was 7 （2-14） weeks, being much longer than that of HC （11 days）. CMV antigen viremia was detected in 12 of the 80 transplanted patients, with a positive rate of 36. 7% in patients with BK viruria and 40. 0% in HC patients. Nine of the 30 HC patients developed acute graft versus host disease （aGVHD） of grade Ⅱ -Ⅳ （30.0% ）. BK virus was not detected in the urine of the remainimg two HC patients and the 20 control subjects as well as in all the blood samples. Univariate analysis indicated that CMV viremia and aGVHD of grade Ⅱ -Ⅳ were associated with the occurrence of BK viruria. Conclusions BK viruria is the main cause of the late-onset HC after HSCT. CMV infection and aGVHD may contribute to the occurrence of HC associatieg with BK virus.