Cytomegalovirus-Specific Immunity Recovers More Slowly after Cord Blood Transplantation Compared with Matched Sibling Donor Allogeneic Transplantation

Rapid quantitative recovery of natural killer (NK) cells, but slower recovery of T cell subsets along with frequent viral infections are reported after umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) compared with matched sibling donor (MSD) HCT. However, whether the increased propensity for viral infections is also a result of slower recovery of virus-specific immunity after UCB HCT compared with MSD HCT remains unclear. In this study, we examined the differences in the function of virus-specific peripheral blood mononuclear cells (PBMCs) after UCB HCT (n = 17) compared with MSD HCT (n = 9) using previously collected patient blood samples at various time points post-transplantation. An IFN-γ enzyme-linked immune absorbent spot (ELISpot) assay was used to quantify the PBMC frequencies that secrete IFN-γ in response to 11 immunopeptides from 5 common viruses. We included patients who received the same reduced-intensity conditioning regimen without antithymocyte globulin, received no systemic glucocorticoids, and had no relapse or acute/chronic graft-versus-host disease within 1 year after HCT. The cytomegalovirus (CMV)-reactive PBMC frequencies were higher in CMV seropositive patients compared with CMV seronegative patients after HCT. Among CMV seropositive patients, the frequency of CMV-reactive PBMC was lower after UCB HCT compared with MSD HCT throughout 1 year post-transplantation. We observed no differences in virus-specific PBMC responses toward human herpesvirus 6, Epstein-Barr virus, BK virus, and adenovirus antigens between UCB HCT recipients and MSD HCT recipients. Our data demonstrate that the reconstitution of CMV-specific immunity is slower in CMV seropositive UCB HCT recipients compared with MSD HCT recipients, in contrast to other viruses, which had similar recoveries in the 2 groups. These study findings support the implementation of more potent prophylactic strategies for preventing CMV reactivation in CMV seropositive patients undergoing UCB HCT.