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15 June 2006

Volume 42, Number 12
Clinical Infectious Diseases 2006;42:1743–1748
© 2006 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2006/4212-0014$15.00
DOI: 10.1086/503838
MAJOR 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,1,a

Jayant S. Kalpoe,2,a

Robbert G. M. Bredius,1

Eric C. Claas,2

Aloys C. M. Kroes,2

Andrew D. Hislop,4

Debbie van Baarle,3

R. Maarten Egeler,1

Maarten J. D. van Tol,1 and

Arjan C. Lankester1

Departments of 1Pediatrics and 2Medical Microbiology, Leiden University Medical Center, Leiden, and 3Department of Immunology, University Medical Center, Utrecht, The Netherlands; and 4 Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom

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.

Received 11 October 2005; accepted 27 January 2006; electronically published 4 May 2006.

  • (See the editorial commentary by Bitan on pages 1749–50)

Reprints or correspondence: Dr. Arjan C. Lankester, Dept. of Pediatrics/BMT Unit, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands ().

Cited by

K Masjosthusmann, K Ehlert, B R Eing, J Roth, G Koehler, H Juergens, M Fruehwald, A H Groll. (2009) Delay in B-lymphocyte recovery and function following rituximab for EBV-associated lymphoproliferative disease early post-allogeneic hematopoietic SCT. Bone Marrow Transplantation 43:9, 679-684
Online publication date: 1-Jun-2009.
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Ellen Meijer, Jan J Cornelissen. (2008) Epstein–Barr virus-associated lymphoproliferative disease after allogeneic haematopoietic stem cell transplantation: molecular monitoring and early treatment of high-risk patients. Current Opinion in Hematology 15:6, 576-585
Online publication date: 1-Dec-2008.
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Hiroshi Kimura, Yoshinori Ito, Ritsuro Suzuki, Yukihiro Nishiyama. (2008) Measuring Epstein-Barr virus (EBV) load: the significance and application for each EBV-associated disease. Reviews in Medical Virology 18:5, 305-319
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S Ocheni, N Kroeger, T Zabelina, I Sobottka, F Ayuk, C Wolschke, A Muth, H Lellek, L Petersen, R Erttmann, H Kabisch, A R Zander, U Bacher. (2008) EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT. Bone Marrow Transplantation 42:3, 181-186
Online publication date: 1-Sep-2008.
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Astrid Meerbach, Peter Wutzler, Ralf Häfer, Felix Zintl, Bernd Gruhn. (2008) Monitoring of Epstein-Barr virus load after hematopoietic stem cell transplantation for early intervention in post-transplant lymphoproliferative disease. Journal of Medical Virology 80:3, 441-454
Online publication date: 1-Apr-2008.
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B. Z. Katz, E. Pahl, S. E. Crawford, M. C. Kostyk, S. Rodgers, R. Seshadri, M. Proytcheva, S. Pophal. (2007) Case?control study of risk factors for the development of post-transplant lymphoproliferative disease in a pediatric heart transplant cohort. Pediatric Transplantation 11:1, 58-65
Online publication date: 1-Mar-2007.
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Menachem Bitan. (2006) Editorial Commentary: Paving the Way Toward a Better Understanding of Viral T Cell Interactions after Stem Cell Transplantation. Clinical Infectious Diseases 42:12, 1749-1750
Online publication date: 15-Jun-2006.
Citation-Full Text-PDF Version (47 kB)

  • N.E.A. and R.G.M.B. contributed equally to this article.

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