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 Journal Article

  

Authors:	Meij, P.; van Esser, J. W. J.; Niesters, H. G. M.; van Baarle, D.; Miedema, F.; Blake, N.; Rickinson, A. B.; Leiner, I.; Pamer, E.; Löwenberg, B.; Cornelissen, J. J.; Gratama, J. W.
Article Title:	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
Abstract:	Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes are considered pivotal to prevent lymphoproliferative disease (LPD) in allogeneic stem cell transplantation (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 after 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 (le, more than 1000 genome equivalents [geq] per milliliter). Nine of these 25 patients progressed to EBV-LPD. CD8(+) 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 after 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 = .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 may identity a subgroup at very high risk for EBV-LPD and supports that EBV-specific CD8(+) T cells protect SCT recipients from progressive, EBV. reactivation and EBV-LPD. (C) 2003 by The American Society of Hematology.
Keywords:	infection; cytomegalovirus; reconstitution; responses; prevention; disorders; frequency; viral load; recipients; bone-marrow transplantation
Journal Title:	Blood
Volume:	101
Issue:	11
ISSN:	0006-4971
Publisher:	American Society of Hematology
Date Published:	2003-06-01
Start Page:	4290
End Page:	4297
Language:	English
ACCESSION:	WOS:000183072800019
DOI:	10.1182/blood-2002-10-3001
PROVIDER:	wos
PUBMED:	12576337
Notes:	Article -- Source: Wos

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