Timing of CMV-specific effector memory T cells predicts viral replication and survival after allogeneic hematopoietic stem cell transplantation

Transpl Int. 2014 Dec;27(12):1253-62. doi: 10.1111/tri.12406. Epub 2014 Oct 21.

Abstract

The aim of this study was to characterize timing, kinetic, and magnitude of CMV-specific immune response after hematopoietic stem cell transplantation (HSCT) and its ability to predict CMV replication and clinical outcomes. Using cell surface and intracellular cytokine staining by flow cytometry, CMV-specific T-cell response was measured in blood, while CMV viral load and chimerism were determined by real-time PCR. Patients that reconstituted CMV-specific T-cell response within 6 weeks after Allo-SCT showed a more robust immune response (CD8(+) : 0.7 cells/μl vs. 0.3/μl; P-value = 0.01), less incidence of CMV replication (33% vs. 89.5%; P-value = 0.007), reduced viral loads (1.81 log copies/ml vs. 0 copies/ml; P-value = 0.04), and better overall survival (72%; CI: 0.53-0.96 vs. 42% CI: 0.24-0.71; P-value = 0.07) than patients with a delayed immune reconstitution. Viremic patients had significantly higher transplant-related mortality than nonviremic patients after 1 year (33% CI: 0.15-0.52 vs. 0% CI: 0.05-0.34; P-value = 0.01). Risk factors independently associated with viral replication were receptor pretransplant CMV-positive serostatus (P-value = 0.02) and acquiring CMV-specific T-cell response after 6 weeks post-transplantation (P-value = 0.009). In conclusion, timing of acquiring a positive CMV-specific T-cell immune response after transplantation may identify patients with different risk for viral replication and different clinical outcomes, including survival.

Keywords: allogeneic stem cell transplantation; cytomegalovirus infection; cytomegalovirus-specific immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Antiviral Agents / therapeutic use
  • Cytomegalovirus / immunology*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / etiology
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / mortality
  • Female
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunologic Memory*
  • Male
  • Middle Aged
  • Postoperative Complications / drug therapy
  • Postoperative Complications / etiology
  • Postoperative Complications / immunology*
  • Postoperative Complications / mortality
  • Prospective Studies
  • T-Cell Antigen Receptor Specificity
  • T-Lymphocyte Subsets / immunology*
  • Time Factors
  • Viral Load
  • Viremia / etiology
  • Viremia / immunology*
  • Virus Activation
  • Virus Replication
  • Young Adult

Substances

  • Antiviral Agents