CMV infection combined with acute GVHD associated with poor CD8+ T-cell immune reconstitution and poor prognosis post-HLA-matched allo-HSCT

Abstract

Cytomegalovirus (CMV) infection and acute graft-versus-host disease (aGVHD) are two major complications that contribute to a poor prognosis after hematopoietic stem cell transplantation (HSCT). Superior early immune reconstitution (IR) is associated with improved survival after HSCT. However, when all three factors, CMV infection, aGVHD, and IR, are concomitantly considered, the effects of the triple events on HSCT are still unknown and should be studied further. Thus we enrolled 185 patients who were diagnosed as hematological malignancies and treated with HLA-matched sibling transplantation (MST) between January 2010 and December 2014, of whom 83 were positive for CMV infection and 82 had aGVHD. Results showed that patients with both aGVHD and CMV infection had significantly higher non-relapse mortality (NRM), lower overall survival (OS), and delayed CD8+ T-cell IR. Multivariate analyses showed that both aGVHD combined with CMV infection and delayed CD8+ T-cell IR were independent risk factors for post-MST prognosis. Recurrent CMV infections are associated with poor CD8+ T-cell reconstitution. However, superior IR could protect against the negative effects of aGVHD and CMV infection on the transplant outcomes.

The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping

“…CMV-CTL reconstitution is often accompanied by a reduction in naive T cells and a stronger immune response, both of which also reflect the possible correlation between CMV and GVHD and the increased risk of subsequent opportunistic infections [ 46 ]. Patients with both aGVHD and CMV reactivation had significantly higher NRM and poorer OS [ 10 , 47 ]. Because infections with CMV and GVHD are the most common complications and account for most of the deaths following allo-HSCT, it is necessary to clarify the relationship between GVHD and CMV reactivation after allo-HSCT.…”

Early T-cell reconstitution predicts risk of EBV reactivation after allogeneic hematopoietic stem cell transplantation

“…Adaptive immunity is the core determinant for EBV prevention [ 39 – 41 ]. Several factors have a role in affecting immune recovery after allo-HSCT, spanning donor age, donor gender, intensive chemotherapy, GvHD prophylaxis, and conditioning regimens [ 42 – 45 ]. T cell recovery after allo-HSCT differs across individuals, and immune-monitoring might help to predict the risk of EBV reactivation shortly after allo-HSCT.…”

Donor aKIR genes influence the risk of EBV and CMV reactivation after anti‐thymocyte globulin‐based haploidentical hematopoietic stem cell transplantation

“…Patients developing CMV viremia experienced a lower GRFS. One possible reason is that viral infection changes the overall immune recovery 46,47 . Jeljeli et al reported that CMV reactivation boosted the expansion of CD8 + T cells, primarily CD28 − CD8 + T‐cells, CD45RA − CD4 + T‐cell and NK cell, which might fuel the development of GVHD.…”

“…One possible reason is that viral infection changes the overall immune recovery. 46,47 Jeljeli et al reported that CMV reactivation boosted the expansion of CD8 + T cells, primarily CD28 À CD8 + T-cells, CD45RA À CD4 + T-cell and NK cell, which might fuel the development of GVHD. EBVinfected cells could be hyperproliferative and lead to immune dysfuction.…”