Clinical Study On Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation In26Patients With Primary Immunodeficiency Diseases

Objectives Primary immunodeficiency diseases(PID)are a group ofinherited disorders characterized by severe impairment of the innate oradaptive immune systems.The clinical manifestations are repeated andchronic infection、autoimmunity and malignancy. Hematopoietic stem celltransplantation(HSCT)is the definitive therapy for a variety of PID toachieve immuno-reconstitution. CMV infection represents the mostcommon viral infection leading to mortality in patients undergoing HSCT.The aim of this study was to explore the risk factors and control measuresof cytomegalovirus(CMV)infection after hematopoietic stem celltransplantion(HSCT)in children with primary immunodeficiencydiseases(PID).Methods We retrospectively analyzed results from26patients withPID-Wiskott-Aldrich syndrome (WAS, n=20)，severe combinedimmunodeficiency (SCID, n=1), X-linked chronic granulomatousdisease(XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June2007to December2012in our center. Twenty-two patients received umbilical cord bloodtransplantation and four patients received HLA-identical sibling bonemarrow transplantion. Most patients received myeloablative conditioningwith busulphan(BU)and cyclophosphamide(CY)while the patient withSCID received reduced-intensity conditioning. GVHD prophylaxisconsisted of cyclosporin A(CsA) and methylprednisolone(MP), switchingCsA to FK506if necessary. Serologic studies(ELISA)and weekly CMVinfection surveillance(quantitative PCR,qPCR)were routinely performedbefore and after HSCT.Antiviral treatments include Ganciclovir or forcarnetwere intitiated based on the early detection of active CMV infection.Results All26patients were male, the median age at HSCT was26.5months(range7~77months).At a median follow up of24months(range5~66months),the5-year overall survival rate was(75.0±9.0)%.CMVinfection occurred in42.3%(11of26)of the patients,Two of them developedCMV-associated interstitial pneumonia(CMV-IP).Thirteen patients were diagnosed as CMV latent pre-transplantinfection. CMV-IgG and CMV DNA both positive were detected at thesame time in five cases. CMV DNA positive only were found in fourpatients; CMV post-transplant active infection occurred in three of them.Eleven patients were diagnosed as CMV post-transplant activeinfection.CMV-DNA turned negative after pre-empty therapy in nine of them.Two patients developed CMV-IP and aGVHD(grades II-III) and thendied of respiratory failure.Univariate analysis revealed that the incidence of pre-transplant CMVinfection between with and without CMV activation groups after HSCT wassignificantly different(62.5%vs10.0%,P=0.010).Additional variables suchas stem-cell sources,donor type, HLA disparity and acute GVHD were notassociated with CMV infection（all P values>0.05）.Conclusions Univariate analysis revealed that CMV infection is onerisk factor of CMV active infection post HSCT,so it was significant toevaluate CMV infection status before HSCT. Urine test by qPCR wasimportant to improve early clinical diagnosis. Drug-resistance should bealert when persistent viral replication was existed after more than3weeksof appropriate antiviral treatment. Maribavir and CMX-001etc. may bringhopes in the future.