The Research Of Monitoring Cytomegalovirus Infection In Hematopoietic Stem Cell Transplant Recipients By Fluorescent Quantitative PCR Assay And Preemptive Therapy

Objective Human cytomegalovirus(HCMV) is a member ofβhuman herpesvirus with double-stranded linear DNA. In developed countries the overall seroprevalence is 30-70%. Following primary infection, the virus establishes latent infection in health adult. Virus reactivation occurs when the immune function are suppressed. Some cases may develop into HCMV disease(i.e. interstitial pneumonia, enteritis, retinitis) .HCMV remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant(allo-HSCT) recipients. The common strategy is universal prophylaxis, means all seropositive recipients are given antiviral prophylaxis. This can significantly reduce HCMV disease. But it is a high-cost strategy and may lead to marrow suppression. Preemptive therapy means antiviral treatment is initiated when HCMV reactivation is detected. The advantages for this management of HCMV infection include avoiding unnecessary therapy, reducing the number of patients exposed to antiviral toxicity, andmaximizing the cost:benefit ratio. It depends on the quick, sensitive and reliable method which can monitor HCMV reactivated infection. The objective of this study is to monitor the copies of HCMV-DNA in allo-HSCT recipients by Fluorescent Quantitative PCR(FQ-PCR) assay, to learn about the infection condition in allo-HSCT recipients, to decision if the reactivated infection is existed and preemptive therapy is needed. Above all,to investigate the superiority of universal prophylaxis and preemptive therapy and to make a comparison between plasma FQ-PCR and leukocytic FQ-PCR.Methods A total of 23 patients underwent allogeneic hematopoietic stem cell transplantation at West China Hospital from September 2004 to April 2006. They were tested by plasma FQ-PCR, leukocytic FQ-PCR and serological assay before transplantation. Recipients were routinely monitored by plasma FQ-PCR and leukocytic FQ-PCR every 2 weeks(from engraftment to day +180). Preemptive therapy was initiated when HCMC-DNA> 10~3 copies/ml by plasma FQ-PCR with intravenous GCV 5mg/kg/twice daily until HCMC-DNA<10~3/ml copies. Statistical analysis of plasma FQ-PCR and leukocytic FQ-PCR was performed by chi-square test.Results Among 23 patients, 22 were positive for HCMV-IgG and 1 was positive for HCMV-IgM. None was found to be positive by plasma and leukocytic FQ-PCR before transplantion.14 patients were found to be positive by plasma FQ-PCR and 16 were by leukocytic FQ-PCR post transplantation. Among 14 plasma FQ-PCR positive patients, 11 initiated preemptive therapy. Two of these 11 patients developed into HCMV disease (interstitial pneumonia). HCMV disease had no evidence in 9 plasma FQ-PCR negative patients.Conclusion This study indicates that HCMV infection is one of common complications in allo-HSCT recipients, which occurs mostly during 30 to 60 days after transplantation. FQ-PCR is a useful method for early and rapid detection of HCMV infection in allo-HSCT recipients. Preemptive therapy based on copies of HCMV-DNA can reduce HCMV diseases just like universal prophylaxis. At the same time, it also can reduce the side effects of antiviral drugs, avoid unnecessary therapy and maximize the cost : benefit ratio. Leukocytic FQ-PCR has higher positive ratio than plasma FQ-PCR. But plasma FQ-PCR is simple and easy to carry out.