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.

Abstract

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/microL) 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.

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@article{Annels2006ManagementOE, title={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.}, author={Nicola E. Annels and Joyant S Kalpoe and Robbert G. M. Bredius and Eric C . J . Claas and Aloys C. M. Kroes and Andrew D Hislop and Debbie van Baarle and Rudolph Maarten Egeler and Maarten J D van Tol and Arjan C Lankester}, journal={Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, year={2006}, volume={42 12}, pages={1743-8} }