Background: Viral infections are a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The effect of herpesvirus infections in human cytomegalovirus (HCMV)-seropositive (IgG-positive/IgM-negative) HSCT recipients remains poorly understood. The risk factors associated with Epstein-Barr virus (EBV), HCMV, and human herpes virus type 6 (HHV-6) infections after HSCT, both alone and in combination, were investigated in this study.

Methods: Peripheral blood specimens were collected from 44 HSCT recipients and examined for viral DNA using quantitative fluorescence PCR assays. Risk factors for EBV, HCMV, and HHV-6 infections were analyzed by binary logistic regression, and relationships between these viruses were analyzed using the Chi-square test.

Results: EBV, HCMV, and HHV-6 were detected in 50%, 45.45%, and 25% of HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients, respectively. Male sex (p=0.007) and conditioning regimens including anti-thymocyte globulin (ATG) (p=0.034) were strongly associated with an increased risk of EBV infection. Graft-versus-host disease (GVHD) prophylaxis with corticosteroids was a risk factor for both EBV (p=0.013) and HCMV (p=0.040) infections, while EBV infection (p=0.029) was found to be an independent risk factor for HHV-6 infection. Pre-existing HHV-6 infection was associated with lower rates of HCMV infection (p=0.002); similarly, pre-existing HCMV infection was protective against HHV-6 infection (p=0.036).

Conclusions: HCMV-seropositive (IgG-positive/IgM-negative) HSCT recipients exhibited a high rate of herpesvirus infections, particularly EBV. ATG and male sex were strongly associated with an increased risk of EBV infection. GVHD prophylaxis with prednisone was found to affect both EBV and HCMV infections. Prior infection with EBV was shown to promote HHV-6 infection. Taken together, these data highlight the need for active monitoring of herpesvirus infections in patients undergoing HSCT.