Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell–depleted SCT

Author:

van Esser Joost W. J.1,van der Holt Bronno1,Meijer Ellen1,Niesters Hubert G. M.1,Trenschel Rudolf1,Thijsen Steven F. T.1,van Loon Anton M.1,Frassoni Francesco1,Bacigalupo Andrea1,Schaefer Ulrich W.1,Osterhaus Albert D. M. E.1,Gratama Jan Willem1,Löwenberg Bob1,Verdonck Leo F.1,Cornelissen Jan J.1

Affiliation:

1. From the Departments of Hematology, Statistics, Virology, and Medical and Tumor Immunology, University Hospital Rotterdam/Daniel den Hoed Cancer Center, The Netherlands; Departments of Hematology and Virology, University Medical Center Utrecht, The Netherlands; Clinic of Bone Marrow Transplantation, University Hospital Essen, Germany; and Department of Hematology, Ospedale San Martino, Genoa, Italy.

Abstract

Reactivation of the Epstein-Barr virus (EBV) after allogeneic stem cell transplantation (allo-SCT) may evoke a protective cellular immune response or may be complicated by the development of EBV-lymphoproliferative disease (EBV-LPD). So far, very little is known about the incidence, recurrence, and sequelae of EBV reactivation following allo-SCT. EBV reactivation was retrospectively monitored in 85 EBV-seropositive recipients of a T-cell–depleted (TCD) allo-SCT and 65 EBV-seropositive recipients of an unmanipulated allo-SCT. Viral reactivation (more than 50 EBV genome equivalents [gEq]/mL) was monitored frequently by quantitative real-time plasma polymerase chain reaction until day 180 after SCT. Probabilities of developing viral reactivation were high after both unmanipulated and TCD-allogeneic SCT (31% ± 6% versus 65% ± 7%, respectively). A high CD34+ cell number of the graft appeared as a novel significant predictor (P = .001) for EBV reactivation. Recurrent reactivation was observed more frequently in recipients of a TCD graft, and EBV-LPD occurred only after TCD-SCT. High-risk status, TCD, and use of antithymocyte globulin were predictive for developing EBV-LPD. Plasma EBV DNA quantitatively predicted EBV-LPD. The positive and negative predictive values of a viral load of 1000 gEq/mL were, respectively, 39% and 100% after TCD. Treatment-related mortality did not differ significantly between TCD and non-TCD transplants, but the incidence of chronic graft-versus-host disease was significantly less in TCD patients. It is concluded that EBV reactivation occurs frequently after TCD and unmanipulated allo-SCT, especially in recipients of grafts with high CD34+ cell counts. EBV-LPD, however, occurred only after TCD, and EBV load quantitatively predicted EBV-LPD in recipients of a TCD graft.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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