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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-10-3001. This Article Full Text (PDF) All Versions of this Article: 2002-10-3001v1 101/11/4290    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Meij, P. Articles by Gratama, J. W Search for Related Content PubMed PubMed Citation Articles by Meij, P. Articles by Gratama, J. W Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted October 23, 2002 Accepted January 23, 2003 Impaired recovery of Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease Pauline Meij, Joost W J van Esser, Hubert G M Niesters, Debbie van Baarle, Frank Miedema, Neil Blake, Alan B Rickinson, Ingrid Leiner, Eric Pamer, Bob Lowenberg, Jan J Cornelissen, and Jan W Gratama* Department of Internal Oncology, Erasmus MC, Rotterdam, The Netherlands Department of Hematology, Erasmus MC, Rotterdam, The Netherlands Department of Virology, Erasmus MC, Rotterdam, The Netherlands Department of Clinical Viro-Immunology, Sanquin Research at CLB, and Landsteiner Laboratory AMC, Amsterdam, The Netherlands Department of Medical Microbiology, University of Liverpool, Liverpool, United Kingdom CRC Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom Infectious Disease Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA * Corresponding author; email: gratama{at}immh.azr.nl. Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes are considered pivotal to prevent lymphoproliferative disease (LPD) in allogeneic stem cell transplant (SCT) recipients. We evaluated the recovery of EBV-specific CD8+ T cells after partially T-cell-depleted SCT, and studied the interaction between EBV-specific CD8+ T cells, EBV reactivation and EBV-LPD. EBV-specific CD8+ T cells were enumerated using 12 class I HLA tetramers presenting peptides derived from 7 EBV proteins. Blood samples were taken at regular intervals post SCT in 61 patients and EBV DNA levels were assessed by real-time polymerase chain reaction. Forty-five patients showed EBV reactivation, including 25 with high-level reactivation (i.e., >1,000 geq/ml). Nine of these 25 patients progressed to EBV-LPD. CD8+ T cells specific for latent or lytic EBV epitopes repopulated the peripheral blood at largely similar rates. In most patients, EBV-specific CD8+ T-cell counts had returned to normal levels within 6 months post SCT. Concurrently, the incidence of EBV reactivations clearly decreased. Patients with insufficient EBV-specific CD8+ T-cell recovery were at high risk for EBV reactivation in the first 6 months after SCT. Failure to detect EBV-specific CD8+ T cells in patients with high-level reactivation was associated with the subsequent development of EBV-LPD (P = 0.048). Consequently, the earlier defined positive predictive value of approximately 40%, based on high-level EBV reactivation only, increased to 100% in patients without detectable EBV-specific CD8+ T cells. Thus, impaired recovery of EBV-specific CD8+ T cells in patients with high-level EBV reactivation identifies a subgroup at extremely high risk for EBV-LPD, and supports that EBV-specific CD8+ T cells protect SCT recipients from progressive EBV reactivation and EBV-LPD. 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