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

Abstract

Background: Rapid quantitative recovery of NK cells but slower recovery of T-cell subsets along with frequent viral infections are reported after umbilical cord blood (UCB) compared with matched sibling donor (MSD) hematopoietic cell transplantation (HCT). However, it remains unclear whether increased propensity for viral infections is also a result of slower recovery of virus-specific immunity after UCB as compared to MSD HCT.

Objectives: We examined the differences in the function of virus-specific peripheral blood mononuclear cells (PBMC) after UCB (N=17) vs. MSD (N=9) using previously collected patient blood samples at various time points after HCT.

Methods: Interferon-gamma (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 the patients who received the same reduced intensity conditioning regimen without ATG, no systemic glucocorticoids and had no relapse or acute/chronic graft-versus-host disease within 1 year after HCT.

Results: The CMV-reactive PBMC frequencies were higher in CMV seropositive vs. seronegative patients after HCT. Among CMV seropositive patients, the frequency of CMV-reactive PBMC was lower after UCB compared to MSD throughout one year of HCT. We observed no differences in virus-specific PBMC responses towards HHV6, EBV, BK, and adenovirus antigens between UCB and MSD.

Conclusion: Our data demonstrate that the reconstitution of CMV-specific immunity is slower in CMV seropositive recipients of UCB vs. MSD HCT in contrast to other viruses which had similar recoveries. These study findings support implementation of more potent prophylactic strategies for preventing CMV reactivation in CMV seropositive patients receiving UCB HCT.

Keywords: IFN-γ ELISpot; hematopoietic cell transplantation (HCT); immune reconstitution; matched sibling donor (MSD); umbilical cord blood (UCB).

Figure.. Virus-specific immune reconstitution after UCB vs. MSD HCT by CMV serostatus

The boxes show the interquartile range of spot-forming cell count (SFC) per 100,000 PBMC specific to each viral antigen by MSD vs. UCB donor types and by CMV serostatus. The bold horizontal lines inside the boxes and the numbers at the bottom of each panel indicate the median SFC per 100,000 PBMC; p-values on top compare the donor type/CMV serostatus groups. The whiskers represent 1.53 the height of the box (or minimum/maximum values if there is no value in that range); and the circles indicate the outliers. The individual figures show the SFC specific to (A) CMV_IE1 peptide by donor type and CMV serostatus; (B) CMV_IE1 peptide in CMV seropositive patients by CMV reactivation status; (C) CMVA_PP65 peptide by donor type and CMV serostatus; (D) CMVA_PP65 peptide in CMV seropositive patients by CMV reactivation status; (E) HHV6_U90 by donor type and CMV serostatus; (F) EBV_EBNA1 peptide by donor type and CMV serostatus, the results against EBV_LMP2 and EBV_BZLF1 peptides were similar to EBV_EBNA1 peptide (not shown); (G) BKV_LTA peptide by donor type and CMV serostatus, the results against BKV_VP1 peptide was similar to BKV_LTA (data not shown); and (H) HAdV3 peptide by donor type and CMV serostatus, the results against HAdV5 peptide was similar to HAdV3 (data not shown).