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Epstein‐Barr virus load in whole blood is associated with immunosuppression,but not with post‐transplant lymphoproliferative disease in stable adult heart transplant patients
Authors:Andreas O Doesch  Mathias Konstandin  Sultan Celik  Arnt Kristen  Lutz Frankenstein  Falk‐Udo Sack  Philipp Schnabel  Paul Schnitzler  Hugo A Katus  Thomas J Dengler
Institution:1. Department of Cardiology, University of Heidelberg, Heidelberg, Germany;2. Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany;3. Department of Pathology, University of Heidelberg, Heidelberg, Germany;4. Institute of Virology, University of Heidelberg, Heidelberg, Germany
Abstract:Development of Epstein‐Barr virus (EBV)‐associated post‐transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real‐time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty‐seven patients (39.0% of total) had a positive EBV PCR at initial examination median 4.9 (range 1.1–16.9) years post‐HTX]. In follow‐up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 ± 70.2 vs. 119.6 ± 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.
Keywords:Epstein‐Barr virus  heart transplantation  post‐transplant lymphoproliferative disease  real‐time PCR
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