Impact of Cytomegalovirus (CMV) Reactivation after Umbilical Cord Blood Transplantation

Abstract

This study investigated the impact of pre-transplant CMV serostatus and post-transplant CMV reactivation and disease on umbilical cord blood transplant (UCBT) outcomes. Between 1994 and 2007, 332 patients with hematologic malignancies underwent UCBT and 54% were CMV seropositive. Pre-transplant recipient CMV serostatus had no impact on acute or chronic GVHD, relapse, DFS or OS. There was a trend toward greater day 100 TRM in CMV seropositive recipients (p=0.07). CMV reactivation occurred in 51% (92/180) of patients with no difference in myeloablative vs. RIC recipients (p=0.33). Similarly, reactivation was not influenced by the number of UCB units transplanted, the degree of HLA disparity, the CD34+ or CD3+ cell dose or donor KIR gene haplotype. Rapid lymphocyte recovery was associated with CMV reactivation (p=0.02). CMV reactivation was not associated with acute (p=0.97) or chronic GVHD (p=0.65), nor did it impact TRM (p=0.88), relapse (p=0.62) or survival (p=0.78). CMV disease occurred in 13.8% of the CMV seropositive patients resulting in higher TRM (p=0.01) and lower OS (p=0.02). Thus, while recipient CMV serostatus and CMV reactivation have little demonstrable impact on UCB transplant outcomes, the development of CMV disease remains a risk, associated with inferior outcomes.

Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function

“…It is also possible that the lower risk of relapse reported in UCB transplantation 33 is associated with CMV reactivation. 34 CMV infection may induce expression of a ligand that activates either CD8 ϩ T cells and/or NK cells. Our data support the possibility that CMV infection may induce NK cells with increased potential to eliminate residual leukemic blasts.…”

The role of the thymus in T-cell immune reconstitution after umbilical cord blood transplantation

“…12,[56][57][58][59][60] Cytomegalovirus (CMV) is the most frequent opportunistic pathogen thought to contribute significantly to HSCT morbidity and mortality. 61 The CMV source after UCBT is almost exclusively of host origin because the incidence of congenital CMV infection is very low.…”

Reconstitution of Protective Immune Responses against Cytomegalovirus and Varicella Zoster Virus Does Not Require Disease Development in Pediatric Recipients of Umbilical Cord Blood Transplantation

“…Development of anti-CMV responses in the absence of detectable viral replication was confirmed by staining with MHCpeptide tetramers. Reports showed that CMV infection can occur in CMV-seronegative patients receiving CMV-seronegative grafts, with an incidence ranging from 1.2 to 12% in the first 3 mo posttransplantation (10,13,22,62). However, to our knowledge, kinetics of antiviral immune reconstitution were never assessed in CMV-seronegative patients receiving CMV-seronegative grafts.…”

“…Major advantages of UCBT include a low incidence of graft-versus-host disease (GvHD) (4) and an efficient graft-versusleukemia effect (5) graftment, late reconstitution of the CD8 + T cell subset, and a higher incidence of opportunistic infections in the first 3-6 mo posttransplantation that results in higher morbidity and mortality relative to BMT during this period (6)(7)(8). In particular, CMV and varicella zoster virus (VZV) are important causes of opportunistic infections, and infections with these pathogens are observed more frequently in UCBT recipients than in BMT recipients (9,10).…”