Clinical Significance Of Dynamic Monitoring EBV, CMV And BKV Infection In Patients After Bone Marrow Transplantation

Objective: Detecting the EBV(Epstein-Barr virus),CMV(Cytomegalovirus)and BKV(BK virus)virus load in blood and urine from patients before and after hematopoietic stem cell transplantation by real-time fluorescence quantitation PCR(RT-PCR).Retrospective studies correlated the EBV,CMV and BKV infection with the clinical characteristics of patients before and after transplantation.Method: Monitor the serological virus antibodies in patients after autologous or allogeneic hematopoietic stem cell transplantation(HSCT)and analyze the related clinical data from July 2014 to November 2016.Detecting the virus load of EBV-DNA,CMV-DNA in blood and BKV-DNA in urine by real-time quantitation PCR three weeks before transplantation.The statistical analysis were made by SPSS 19.0,and p<0.05 was considered as statistically significant.Result:1.A total of 83 patients were included in this study.The ratio of male to female was closely to 1:1;the ratio of adult to pediatric patients was 3:1;leukemia patients to non-leukemia patients was about 1:1.2.Serological analysis showed that: the EBV-Ig G antibodies were 100% positive,which suggested that all patients had EBV infection before.While,positive rate of CMV-Ig G were 90.4%,which indicated that the majority of patients had infected from CMV.Among the 61 patients after allogeneic transplantation,1 case was D-/R+(D/R:Donor/Receptor;-/+: negative/ positive),7 cases were D+/R-and 53 cases were D+/R+.And the D-/R+ group suffered from the CMV activation.Moreover,the rate of D+/Rpatients with CMV infection(57.1%)was slightly higher than those of D+/R+ patients(26.4%)(P=0.095).3.The rate of EBV infection was 33.7% analyzed by real-time fluorescence quantitation polymerase chain reaction(RT-PCR),which was significantly higher in allogeneic transplantpatients than that in autologous transplant ones(P=0.004).It was also higher in patients treated with ATG than those without(P=0.000).EBV-related Post-Transplantation Lymphoproliferative Disorders(PTLD)occurred in 2 patients after transplantation(2/83,2.4%).EBV infection significantly reduced the overall survival of patients after transplantation(P=0.0469).4.The rate of CMV infection was 22.9% analyzed by RT-PCR.The incidence of CMV-related diseases was 36.8%(7/19),of which 5 cases diagnosed with respiratory diseases and 2 cases with gastrointestinal system diseases.There was no patients suffered from CMV infection in autologous transplantation;However,the rate of CMV infection in allogeneic transplantation was 31.1%,which was higher in patients with ATG than that in patients without ATG(P=0.003).And the patients with CMV-related diseases were all pretreated with ATG.So were the patients with male donors,in which CMV infection was higher than female donors(P=0.049).5.The rate of BKV infection was 47.0%,of which 24 cases suffered from hemorrhagic cystitis(HC)(61.5%,24/39).And the median duration time of viremia was118 days in HC patients,and 88 days in non-HC patients.The incidence of BK infection in ALL patients was slightly higher than that in AML patients(61.5% vs 46.4%)/Nevertheless,the incidence of HC was significantly lower in ALL than in AML(P=0.026);the rate of BKV infection in allogeneic transplantation was higher than that in autologous transplantation(P=0.002).The incidence of HC in haplo-identical transplantation was significantly higher than that in HLA-matched transplantation(P=0.006).The incidence of hemorrhagic cystitis was significantly higher in transplant patients transfused with both bone marrow and peripheral hematopoietic stem cellsthan those only with peripheral hematopoietic stem cells(P=0.002).Both the rate of BK infection(P=0.01)and the incidence of hemorrhagic cystitis(P=0.002)in patients with ATG were higher than patients without ATG.Conclusion:1.EBV,CMV and BKV are common viral pathogens found in patients after hematopoietic stem cell transplantation.A variety of factors may affect the viral infection or virus activation status in patients after hematopoietic stem cell transplantation.2.The type of transplantation and the application of ATG had significant influence on EB,CMV and BKV infection in patients after hematopoietic stem cell transplantation;The source of stem cells had no significant influence on the incidence of the virus,but could significantly affect the occurrence of EB and BK virus-related diseases;The incidence of BK virus-related hemorrhagic cystitis was significantly influenced by the HLA compatibility and leukemia type,but the BK virus infection rate was not.3.The detection of serologic virus antibodies by ELISA could not describe the actual virus infection accurately,but it played a role on the prediction of the virus activation in patients after transplantation.The detection of virus DNA by RT-PCR was more sensitive,and could monitor the viral DNA copies in blood and urine in transplant patients dynamically.4.Active prophylaxis with antiviral drugs could significantly reduce the post-transplant viral infection and viral-related diseases.