Clinical Study Of Cytomegalovirus Infection After Nonmyeloablativc Allogeneic Peripheral Blood Stem Cell Transplantation

Objective The aim of this study was to analyze the risk factors ofcytomegalovirus (CMV) infection and CMV disease after nonmyeloablative allogeneichematopoietic stem cell transplantation(NST) by means of peripheral blood real timequantitative polymerase chain reaction(RT-PCR). Furthermore, to analyze the factorsimpacting the efficacy of preemptive therapy and the effect on CMV disease incidenceand the overall survival of NST to develop a rational strategies for thediagnosis, monitoring and preemptive treatment of CMV infection.Methods The Clinical data of80patients undergoing NST from Nov.2009to Nov.2012in the military307hospital were retrospectively analyzed.Results The incidence of CMV infection was77.5%(62/80), and the median timefor the first detection of positive CMV-DNA was at day35(17～133) after NST. Thetotal100-day cumulative incidence of CMV disease was11.3%(9/80) after earlypreemptive therapy. Both univariate and multivariate analyses showed Thymoglobulin(ATG，Genzyme Corp.) containing in preparative regimen, other herpesvirus infectionand and fungal infection medical history before NST were the risk factors of CMVinfection after NST. Univariate analysis revealed that CMV viremia and ATG are therisk factors for CMV disease while the same result was not found in the multivariateanalysis. It seems that Ⅱ～Ⅳ0aGVHD is not the risk factor of CMV infection for NST.Among291times of positive peripheral blood leukocyte CMV–DNA detectionsposttransplant,62patients developed CMV infection. Of them,51patients developed1episodes of CMV infection while10patients had2episodes and1patient had3episodes. There was no correlation between the time of CMV infection and the time ofANC engrafted(r=0.005,P=0.597).59out of62patients with new CMV infection received preemptive therapy and the total success efficacy was74.6%(44/59).1out of3patients was naturally cured without treatment.There were two response patterns in thecured patients:12patients quickly responded within2weeks (median9d; range7-14d)while32patients slowly responded after2weeks (median22d;range15-115d). For thecured patients, not the initial but the maximum CMV-DNA had a correlation with thesuccess time.There were no statistic difference of CMV-DNA load between the patientswith or without CMV disease. Both univariate and multivariate analyses showedineffectiveness or severe toxcity of initial treatment of GCV and II～IVoaGVHD arethe adverse factors of preemptive therapy. Univariate analysis also showed CMV-DNAload had a effect on preemptive therapy while the same result was not found in themultivariate analysis. The outcome of preemptive therapy had a significant effect onboth the incidence of CMV disease and the overall survival of NST.Conclusion ATG containing in conditioning regimen might increase the incidence ofboth CMV infection and CMV disease after NST. CMV infection were correlated withother herpesvirus infection and medical history of fungal infection. Peripheral bloodPCR is a very useful and suitable surveillance method for detecting and monitoringCMV infection and guiding preemptive therapy after NST. The outcome of preemptivetherapy will make a difference on the overall outcome of NST.