Journal Article

Management of Epstein-Barr Virus (EBV) Reactivation after Allogeneic Stem Cell Transplantation by Simultaneous Analysis of EBV DNA Load and EBV-Specific T Cell Reconstitution

Nicola E. Annels, Jayant S. Kalpoe, Robbert G. M. Bredius, Eric C. Claas, Aloys C. M. Kroes, Andrew D. Hislop, Debbie van Baarle, R. Maarten Egeler, Maarten J. D. van Tol and Arjan C. Lankester

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 42, issue 12, pages 1743-1748
Published in print June 2006 | ISSN: 1058-4838
Published online June 2006 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/503838
Management of Epstein-Barr Virus (EBV) Reactivation after Allogeneic Stem Cell Transplantation by Simultaneous Analysis of EBV DNA Load and EBV-Specific T Cell Reconstitution

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Background. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies.

Methods. With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients).

Results. In 6 of 8 cases, a significant T cell reconstitution (i.e., a CD3+ T cell count of >300 cells/µL) was documented during EBV reactivation, which included an expansion of EBV-specific memory T cells, as shown by human leukocyte antigen class I tetramer analysis. Additional evidence for the antiviral potential of this T cell reconstitution was obtained prospectively from a cohort of 14 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD. EBV reactivation occurred in 3 patients. Preemptive treatment was successfully withheld for 2 of these patients in light of concurrent (EBV-specific) T cell recovery.

Conclusion. We conclude that analysis of the level of (EBV-specific) T cell reconstitution during EBV reactivation is an important second parameter, in addition to quantification of EBV DNA load, that will be instrumental in a more accurate definition of patients at risk for EBV-LPD who, given their immunoincompetence, will be most certainly dependent on preemptive interventions.

Journal Article.  3244 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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