Clinical Risks Analysis Of EBV Infection For Children Patients With Allogeneic Hematopoietic Stem Cell Transplantation

Objective1?To explore the risk factors of EB virus(Epstein-Barr virus,EBV)infection and reactivation in children after allogeneic hematopoietic stem cell transplantation(Allogeneic hematopoietic stemcell transpalntation,Allo-HSCT),so as to identify high risk factors early in clinic and carry out prevention and treatment as early as possible to prevent disease progression.2?For children with EBV infection,the total survival time(Overall Survival,OS)and event-free survival time(event free survival,EFS)of high copy group after EBV infection were analyzed to explore the prognosis of rituximab preemptive treatment in children with EBV infection,reduce the incidence of lymphoproliferative diseases(post transplantation lymphoproliferative disorder,PTLD)after transplantation and improve the survival rate of children.Methods1?A total of 268 patients who underwent Allo-HSCT,and regularly tested EBV copies in the children's hospital of soochow university from January 1,2016 to December 31,2018 were analyzed retrospectively.The sex,age,type of disease,intensity of pretreatment,use of antithymocyte globulin(Anti-thymocyte globulin,ATG),graft type,stem cell source,acute graft-versus-host disease(acute graft-versus-host disease,aGVHD)and chronic graft-versus-host disease(chronic graft-versus-host disease,cGVHD)were collected,the use of anti-CD20 monoclonal antibody(rituximab)before transplantation,the number of CD34+cells infused,the time of granulocyte implantation and other clinical data,Chi-square analysis and Logistic analysis were used to analyze the correlation between the above factors and the conditions of EBV infection.2?From January 1,2016 to December 31,2018,OS and EFS were retrospectively analyzed in 268 children who underwent Allo-HSCT in the children's hospital of soochow university,EBV infection group and EBV non-infection group.They were divided into 6 groups:a).32 children were treated with rituximab without rituximab in the pretreatment stage,and EBV+-occurred after allo-HSCT;b).The children with EBV associatde syndromes after allo-HSCT without rituximab during preconditioning,and the group without rituximab,there were 110 cases in the group without rituximab;c).There were 83 patients without rituximab in the pretreatment stage and no EBV associatde syndromes occurred in the group treated with rituximab;d).Rituximab was used in the pretreatment stage,EBV+occurred after allo-HSCT,and rituximab was used again in the rituximab group,with a total of 1 case;e).Rituximab was used in the pretreatment stage,EBV+occurred after allo-HSCT,and rituximab was not used in the control group,there were 6 cases in the group without rituximab;f).36 patients without EBV associatde syndromes after allo-HSCT were treated with rituximab during preconditioning.The Kaplan-Meier method was used to analyze the OS and EFS of children with EBV in different groups after the use of rituximab,to observe the therapeutic effect and median recovery time,and to monitor the occurrence of EBV-PTLD.Results1?Among the 268 children,the cumulative incidence of EBV associatde syndromes after Allo-HSCT was 55.5%.The median time of EBV associatde syndromes after transplantation was 42(24,88)days.2?Univariate analysis showed that EBV infection after Allo-HSCT was associated with age,type of disease,intensity of pretreatment,use of ATG,type of transplantation,??? aGVHD,source of stem cells and use of rituximab during preconditioning,but not with sex and cGVHD.In EBV associatde syndromes group,more CD34+cells were infused and neutrophil implantation time was shorter.Multivariate analysis showed that the use of ATG,different sources of donor stem cells and pretreatment were independent risk factors for EBV infection after HSCT,while rituximab was the protective factor for EBV infection.3?After allo HSCT operation,149 children had EBV infection,47 children had high copy number of EBV infection,the incidence was 31.5%.In total,17/47(36.1%)patients experienced high levels of EBV reactivation within 2 weeks after the first EBV-DNA-PCR positive.Of the 47 children with high copy number of EBV,18 were treated with rituximab and no EBV-PTLD occurred,while there was one case of EBV-PTLD in the unused group,and the incidence of EBV-PTLD was 0.37%.4?Among the 68 children,there was no significant difference in OS and EFS between group A,group B and group C.There was no significant difference in OS and EFS between group D,group E and group F.Conclusions1?EBV infection after allo HSCT is closely related to patient's age,_primary disease,pretreatment intensity,ATG use,transplantation type,stem cell source and rituximab use in pretreatment stage.2?The use of ATG,stem cell sources,and the absence of rituximab in the pretreatment phase were independent risk factors for EBV after allo HSCT.3?Pretreatment with rituximab can reduce the incidence rate of EBV-PTLD effectively.