CMV seronegative donors: Effect on clinical severity of CMV infection and reconstitution of CMV-specific immunity

Abstract

Background: Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R⁺D^-) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft.

Methods: We analyzed the duration of CMV reactivations and the incidence of CMV disease in R⁺D^- and R⁺D⁺ patients after alemtuzumab-based T-cell depleted allogeneic stem cell transplantation (TCD alloSCT). To determine the presence of donor-derived primary CMV-specific T-cell responses we analyzed the origin of CMV-specific T-cells in R⁺D^- patients.

Results: The duration of CMV reactivations (54 versus 38 days, respectively, p = 0.048) and the incidence of CMV disease (0.14 versus 0.02, p = 0.003 at 1 year after alloSCT) were higher in R⁺D^- patients compared to R⁺D⁺ patients. In R⁺D^- patients, CMV-specific CD4⁺ and CD8⁺ T-cells were mainly of recipient origin. However, in 53% of R⁺D^- patients donor-derived CMV-specific T-cells were detected within the first year.

Conclusions: In R⁺D^- patients, immunity against CMV was predominantly mediated by recipient T-cells. Nevertheless, donor CMV serostatus significantly influenced the clinical severity of CMV reactivations indicating the role of CMV-specific memory T-cells transferred with the graft, despite the ultimate formation of primary donor-derived CMV-specific T-cell responses in R⁺D^- patients.

Keywords: Alemtuzumab; Allogeneic transplantation; Cell separation; Chimerism; Cytomegalovirus infections; Flow cytometry; Stem cell transplantation; T-lymphocytes.