Virus Infection In Patients After Allogeneic Hematopoietic Stem Cell Transplantation

Part1: Monitoring and clinical analysis of Epstein–Barr virus infectionin patients after allogeneic hematopoietic stem cell transplantationObjective: Discussion the prevalence of Epstein–Barr virus infection inpatients after allo-HSCT, explore the character of EBV infection and use theeffective therapy strategy to improve the long term survival of the patients.Methods: The outcomes of905patients after allo-HSCT from July2011toJuly2014in our hospital, Comparison the incidence of EBV infectionbetween different transplantation type、preconditioning regimen and etc.Results:(1) The905cases of hematologic disease treated with allo-HSCTwere analyzed, including394related matched donors,250relatedhaploidentical donors,233unrelated volunteer donors, and28unrelated cordblood. The occurrence rate of EBV viremia is: Haplo-HSCT21.6%（54/250）,URD-HSCT16.7%（39/233）,Sib-HSCT5.1%（20/394）.(2)A total of118patients were identified with EBV viremia (EBV+). The2-year cumulative occurrence rate was22.1%±1.9%. The2-year overallsurvival (OS) rate was8.2%±2.6%and74.2%±7.1%(P=0.174) respectivelyin EBV+group and EBV-group. And the2-year non-relapse mortality was14.9%±2.4%and19.8%±7.2%(P=0.493) respectively. (3) In118EBV+cases, a total of5patients underwent PTLD and the2-yearcumulative occurrence rate was6.2%±0.3%. None PTLD was observed inEBV-cases. The2-year OS was75.4%±21.7%and71.5%±9.2%(P=0.6612)in patients with PLTD and without PLTD, respectively.(4) In483allo-HSCT patients who underwent HSCT with conditioningregimen including ATG, the EBV viremia rate was19.3%(93/483), whichwas higher than that in whom ATG was not included in conditioning regimen.Of6patients with EBV-DNA copies＞106copies/ml for2times or more,3cases developed to PTLD. However, there were only2cases of PTLD inother112patients with low EBV-DNA burden (P=0.001).(5) Multivariate analysis indicated that condition regimen with TBI(RR=0.001，95%CI0-0.018，P=0.012) and the occurrence time of EBV wasa protective factor for OS of the EBV+patients. Application of rituximabtherapy also could improve the OS of the EBV+patients, although thedifference was not significant (P=0.058).Conclusion:(1) Due to preemptive therapy, there was no significantdifference in2-year OS between EBV+group and EBV-group.(2) The occurrence of PTLD was higher in patients with high EBV-DNAburden. However, among the EBV+patients,2-year OS were similar betweenPTLD group and non-PTLD group.(3) Conditioning regimen including ATG was associated with higher occurrence rate of EBV viremia. Patients with EBV-DNA>106copies/ml for2times or more were susceptible to develop PTLD. The OS was higher inpatients with a myeloablative conditioning regimen with TBI, late occurrenceof EBV viremia and application of rituximab treatment.Part2: Clinical outcomes of allogeneic hematopoietic stem celltransplantation patients with CMV and EBV co-activationObjetctive: To evaluate the impact of CMV and EBV co-activation on theprognosis of transplant patients. Methods: We retrospectively analyzed330consecutive allo-HSCT patients in our department from December,2011toAugust,2013in this study. CMV and EBV DNA were regularly monitored byquantitive PCR from the engraftment of granulocyte to one year aftertransplantation. The incidences of viremia and clinical outcomes wereanalyzed by χ2test and Kaplan-Meier analysis. Results: After a medianfollow-up of16(7～25) months, a total of113patients were identified withCMV viremia (CMV+) alone,82patients with EBV viremia (EBV+) alone,and32patients with CMV and EBV co-activation (CMV/EBV+). Theproportion of patients undergone HLA mismatched transplantation and theones with acute graft-versus-host disease (aGVHD) is significantly higherthan CMV+group or EBV+group. The incidence of PTLD was similar toEBV+group (11.0%vs12.5%，P=0.802), and so as the incidence of CMVdisease when compared to CMV+group (9.4%vs7.1%, P=0.665).2-year overall survival (OS) of CMV+, EBV+and CMV/EBV+group were68.7%,61.5%and62.4%, respectively, and no significant difference were observedbetween CMV/EBV+and the other two groups (P=0.598,0.717). However,the6-month non-relapse mortality (NRM) of CMV/EBV+group wassignificantly higher than that of CMV+and EBV+group (18.7%vs8.9%, P=0.036;18.7%vs8.1%, P=0.032). Conclusion: HLA mismatch transplantsand aGVHD were frequent in CMV and EBV co-activation group. Whencompared to EBV+or CMV+patients, the CMV/EBV+patients had similarincidence of PTLD or CMV disease.2year OS had no statistical differenceamong the three groups. However, the6-month NRM was significantly higherin CMV/EBV+group, which suggested CMV and EBV co-activation was arisk factor for early death of allo-HSCT patients.