异基因造血干细胞移植后长期生存患者CMV 感染的监测

Cytomegalovirus infection monitoring in patients with long-term survival after allogeneic hematopoietic stem cell transplantation

目的：分析异基因造血干细胞移植（ allo-HSCT）后长期生存患者巨细胞病毒（ CMV）感染的状况及危险因素。方法对2008年1月至2011年12月期间在浙江大学附属第一医院进行allo-HSCT的患者应用免疫荧光组织化学法定期监测患者的外周血CMV被膜蛋白（ CMV-pp65）抗原，应用更昔洛韦或磷甲酸钠预防及治疗CMV感染；选择allo-HSCT后存活1年及以上患者共159例，对其临床资料进行回顾性分析。结果159例患者，均为allo-HSCT后长期生存的患者，移植后时间为18～66个月，共检测8047份外周血标本，其中有2553份为阳性。所有患者移植后均有CMV-pp65抗原血症阳性史，移植前、移植后100 d内、第100天到1年以内患者CMV抗原血症阳性率逐渐上升，1年后阳性率逐渐下降，差异有统计学意义（均P＜0．01）。清髓性预处理allo-HSCT患者移植后CMV抗原血症阳性率高于非清髓性预处理患者[32．1％（2386/7439）比27．5％（167/608），P＝0．019]。是否合并有急、慢性移植物抗宿主病（ GVHD）患者间CMV抗原血症阳性率的差异均无统计学意义（均P＞0．05），但Ⅲ～Ⅳ度急性GVHD患者的CMV抗原血症阳性率高于Ⅰ～Ⅱ度患者[35．4％（227/641）比31．0％（1017/3284），P＝0．027]。预处理未应用抗胸腺细胞球蛋白（ATG）患者移植后CMV抗原血症阳性率为高于应用ATG患者[33．4％（1255/3755）比30．2％（1298/4292）， P＝0．002]。 Logistic多因素分析均显示预处理中未应用ATG（OR＝1．174，95％CI：1．068～1．290，P＝0．001）及移植后合并Ⅲ～Ⅳ度急性GVHD（OR＝1．174，95％CI：0．681～0．958，P＝0．014）是移植后发生CMV抗原血症的独立危险因素。结论 allo-HSCT后定期监测CMV抗原有利于及时预防和治疗CMV感染。长期生存患者合并CMV感染可能与预处理方案的选择相关，与GVHD的发生无明显相关，但与急性GVHD的严重程度相关。

Objective To analyze the cytomegalovirus （ CMV） infection status and the risk factors in patients with long-term survival after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods 159 long-term survivors receive allo-HSCT from January 2008 through December 2011 in the Bone Marrow Transplantation Center of Zhejiang University were included, CMV-pp65 antigen in peripheral blood leukocytes was detected by immunofluorescence assay at regular intervals, to retrospectively analyzed the clinical data.Ganciclovir or foscarnet was used for prevent and curative therapy.Results A total of 159 patients with long-term survival at 18-66 months after allo-HSCT were investigated.And 8 047 specimens were detected, including 2 553 positive samples.All patients were at least one time positive for CMV-pp65 antigen after allo-HSCT. The CMV antigen positive rate increased gradually from 100 days after transplantation to within 100 days until 1 year while the positive rate decreased, after 1 year.The difference was statistically significant （ all P ＆lt;0.01 ） . The CMV antigen positive rate in patients after non-myeloablative allo-HSCT （ NST ） and those after myeloablative allo-HSCT were 167/608 （ 27.5%） and 2 386/7 439 （ 32.1%） respectively. The difference was statistically significant （ P =0.019 ） . No statistically significant difference existed between those with acute graft-versus-host disease （ aGVHD） and chronic graft-versus-host disease （cGVHD） （both P＆gt;0.05）.The CMV antigen positive rate in patients withⅠ-Ⅱgrade aGVHD and those withⅢ-Ⅳgrade aGVHD were 1 017/3 284 （ 31.0%） and 227/641 （35.4%） respectively.And it had statistically significant difference （ P =0.027 ） .The CMV antigen positive rate in patients none-used of ATG and those used of ATG were 1 255/3 755 （33.4%） and 1 298/4 292 （ 30.2%） respectively.And it had statistically significant difference （ P =0.002 ） .By Logistic multivariate analysis,the none-use of ATG and Ⅲ-Ⅳgrade aGVHD were the risk factors for CMV antigen positive after allo-HSCT （ OR=1.174,95%CI：1.068 -1.290,P=0.001;OR=1.174,95%CI：0.681 -0.958, P=0.014）.Conclusions Regular monitoring of CMV-pp65 antigen after allo-HSCT is quite necessary for prevent and treat CMV infection in a timely manner.The CMV infection in long-term survival patients may be related to the selection of conditioning regimen, it has no obvious correlation with the incidence of GVHD, but it is associated with the severity of aGVHD.