The clinical value of concomitant Epstein Barr virus (EBV)-DNA load and specific immune reconstitution monitoring after allogeneic hematopoietic stem cell transplantation

Transpl Immunol. 2011 May;24(4):224-32. doi: 10.1016/j.trim.2011.03.002. Epub 2011 Apr 2.

Abstract

Background: Monitoring of EBV DNAemia after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary, but not sufficient, to identify patients at risk of EBV-induced post-transplantation lymphoproliferative disorders (PTLD). Combining this with quantifying EBV-specific cellular immunity was shown to be helpful. In this study, we evaluated the value of IFNγ-Elispot assay in monitoring EBV DNAemia after HSCT.

Methods: EBV-DNA load in whole blood was monitored at least weekly using real-time PCR in 40 recipients of HSCT. Quantitative and qualitative T-cell recoveries, including EBV-specific T-cell quantification by Elispot assay, were studied 60, 100, 180 and 360 days after HSCT.

Results: Among the 35 evaluable patients, 14 (35%) presented EBV DNAemia, only 2/14 (14%) needing pre-emptive treatment with rituximab. The greatest risk factor for EBV DNAemia was the presence of anti-thymocyte globulin (ATG) (p=0.005). EBV-specific cellular immune recovery was monitored by IFNγ-Elispot assay. Using multivariate analysis, four factors were found to significantly influence IFNγ-Elispot results at defined times post-HSCT: EBV DNAemia, young age, global T-cell recovery and severe acute GVHD. In those cases where EBV DNAemia occurred and cleared spontaneously, Elispot results gave more than 1000 spot-forming cells (SFC)/10(6)PBMC.

Conclusion: Elispot assay may be usefully combined with EBV-DNA load monitoring to determine when a patient should receive pre-emptive treatment, or when the clinician should avoid Rituximab use which severely immunocompromises patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Antigens, Viral / immunology
  • Cells, Cultured
  • DNA, Viral / analysis*
  • Enzyme-Linked Immunospot Assay*
  • Hematopoietic Stem Cell Transplantation*
  • Herpesvirus 4, Human / physiology*
  • Immunity, Cellular / drug effects
  • Immunocompromised Host
  • Interferon-gamma / metabolism
  • Lymphoproliferative Disorders / genetics*
  • Lymphoproliferative Disorders / immunology
  • Lymphoproliferative Disorders / prevention & control
  • Lymphoproliferative Disorders / virology
  • Monitoring, Immunologic / methods
  • Reproducibility of Results
  • Rituximab
  • Transplantation, Homologous
  • Viral Load / drug effects

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, Viral
  • DNA, Viral
  • Rituximab
  • Interferon-gamma