Background. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ. Methods. In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease. Results. Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin. Conclusion. Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.
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