Investigation Of The Factors Related To The Infection Of CMV After Allogeneic Hematopoietic Stem Cell Transplantation And CMV Specific T Cells For Adoptive Immunotherapy Of CMV Infection

Part1: Clinical analysis of CMV infection after allogeneichematopoietic stem cell transplantationObjective To investigate the allogeneic hematopoietic stem cell transplantation(allo-HSCT) after cytomegalovirus (CMV) infection related factors. Methods From2011January to2013December in the First Affiliated Hospital of Soochow UniversityDepartment of Hematology received allogeneic hematopoietic stem cell transplantation inpatients with769cases, by quantitative PCR method for detecting the level of CMV-DNA,immunofluorescence staining leukocyte antigen PP65two methods for the detection ofCMV infection diagnosis, retrospective analysis accord with the clinical data of259patients with CMV infection. Results769cases of patients with male, female CMVinfection rates were34.24%and32.93%(P>0.05). The age18years old were stratifiedaccording to the adult, less than18years of age and older than18CMV infection rateswere35%and33.3%(P>0.05). gender and age of graft CMV infection occurred in nostatistical difference; the matched related, unrelated donor, haploidentical hematopoieticstem cell transplantation were compared, the positive rates were24.39%,38.07%,53.29%,(P<0.01), there are significant difference.In2012the application of ganciclovir, foscarnet prophylactic antiviral therapy,compared to allo-HSCT of three years, the infection rate of CMV. In201156.12%,201226.86%,201329%, In2012and2013CMV infection compared2011the incidence ofsignificant difference(P<0.01). took and did not take preventive antiviral therapy of CMVpositive for the first time there are significant difference(P<0.01). In two kinds of means of quantitative detection of CMV-DNA and CMV-PP65, were associated with CMVdisease, CMV disease which occurs with CMV-DNA viral load increased, the infectionrate of CMV increased, CMV disease and positive duration has no significant correlationoccurred early CMV infection positive CMV disease is high in the late stage. Theoccurrence of CMV infection and the occurrence of different degrees of aGVHD analysis,0-I aGVHD CMV infection rate was19.5%II-IV degree aGVHD CMV infection ratewas57.2%(P<0.01). The different hormone dosage methylprednisolone for theconversion of methylprednisolone(MP), different dose hormone statistical analysis foundthat greater than and equal to CMV, positive rate of MP2mg/kg was63.79%, lower thanthat of MP2mg/kg20.67%(P<0.01).the comparison between the two had positive andnegative significant statistical difference. In CMV detection ratio of HC were72.5%and12.16%(P<0.01). Conclusion Large dose steroid hormone is a risk factor for CMVinfection. The related factors of donor gender and age than CMV infection. Unrelateddonor and haploidentical HSCT incidence of CMV infection was higher than that ofcompatriot mismatched HSCT, the risk factors of early application of prophylactic antiviraldrugs to reduce CMV risk CMV infection in the early stage of transplantation, worthy ofrecommendation. CMV-PP65, CMV-DNA two kinds of detection and CMV relateddiseases, CMV-DNA viral load is higher the greater the risk of CMV disease. CMVdisease and CMV infection not associated with duration. Early CMV infection associatedwith HC.Part2: Study on CMV reactivation and obliterative bronchiolitiscorrelation in Allogeneic hematopoietic stem cell transplantationObjective To investigate the CMV infection in allo-HSCT after interaction withBOS. Methods From2011January to2013December in the First Affiliated Hospitalof Soochow University Department of hematology for allogeneic hematopoietic stem celltransplantation in patients with769cases, by fluorescence quantitative PCR method fordetecting the level of CMV-DNA, immunofluorescence staining of pp65in white bloodcell antigen in two kinds of detection method for the diagnosis of CMV infection, CMVinfection in patients with BOS, and no CMV infection in patients with bronchiolitisobliterans were analyzed, to determine whether CMV infection associated with bronchiolitis obliterans, and diagnosed CMV infection patients were grouped, with andwithout BOS group, the clinical data of two subjects were analyzed. Results ConfirmedCMV infection and non infection in CMV patients the incidence of BOS were12.35%and1.56%(P<0.01). In the analysis of quantitative CMV-DNA and CMV positive duration oftwo single factors, BOS and occurrence time of positive, not associated with viral load.(P>0.05). But the occurrence of BOS and CMV infection times, after CMV infectionreactivation BOS, a primary CMV infection BOS ratio increased significantly (P<0.01).Occurrence of BOS increased the ratio of CMV related diseases, CMV disease comparedwith non CMV disease occurrence of BOS had significant difference (P<0.01).Conclusion Allo-HSCT risk factors which cause BOS, CMV infection and CMV diseaseis related to risk factors of note. After HSCT, once the diagnosis of CMV infection, shouldbe applied with adequate dosage and duration, reduce the CMV infection and reactivationof BOS.Part3: Application of CMV specific T cell for the treatment of CMVinfection post allogeneic hematopoietic stem cell transplantionObjective To investigate the CMV specific T cells for adoptive immunotherapyapplied in allo-HSCT after the refractory CMV infection. Method For selectingallo-HSCT after CMV infection in1patients, Post double umbilical cord blood HSCT,the persistent CMV infection, ganciclovir, foscarnet sodium, cidofovir, CMV specificimmunoglobulin are invalid, analysis of T cell subsets, the existence of T cells inhibited inpatients with excessive, The father is haploidentical to the patient and is CMV IgGantibody positive,CMV specific T cells were selectived by using magnetic beads and thepatient received haploidentical CMV specific T cell transfusion. Results Beforeinfusion of CMV-DNA was105copies/ml, after the infusion of CMV-DNA to103copies/ml,CMV infection related control of fever. After the infusion did not induce GVHD, and theinfusion reaction. Conclusion CMV specific T cells is a new treatment option forrefractory CMV infection post allo-HSCT. Specific T cell transfusion is a safe andeffective treatment option, worthy of clinical application.