Skip to main content
Top
Published in: Virology Journal 1/2011

Open Access 01-12-2011 | Research

Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients

Authors: Fausto Baldanti, Vanina Rognoni, Alessandro Cascina, Tiberio Oggionni, Carmine Tinelli, Federica Meloni

Published in: Virology Journal | Issue 1/2011

Login to get access

Abstract

Background

Post-transplant lymphoproliferative disorders (PTLD) are serious complications in lung transplant recipients. No consensus on EBV DNAemia levels predictive of PTLD has been reached. In addition, in many instances EBV DNAemia is determined in patients with suggestive symptoms only.

Methods

The characteristics of five patients with PTLD as well as the prevalence of EBV DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are described.

Results

Twenty-six out of 137 patients (18.9%) were excluded from the analysis because lost at follow-up or dead from PTLD-independent reasons within three months of transplantation. EBV DNA in peripheral blood mononuclear cells (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD-related symptoms, while 28 patients (25.2%) showed no symptoms and were not examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in 30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median time of 270 (range 120-870) days following transplantation. All five PTLD (three large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic lesion) were potentially associated with EBV infection. However, only 3/5 patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 × 105 PBMC in one patient and > 1,000 copies EBV DNA/1 × 105 PBMC in two patients.

Conclusion

A systematic multidisciplinary (clinical, radiologic, virologic and histologic) approach is mandatory for the diagnosis and management of PTLD in lung transplant recipients, while monitoring of symptomatic patients only may provide an incomplete or late picture of the clinical problem. In addition, staining for EBV antigens and quantification of EBV DNA in biopsy specimens should always be performed to understand the role of EBV infection in the pathogenesis of PTLD.
Appendix
Available only for authorised users
Literature
1.
go back to reference Opelz G, Dohler B: Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004, 4: 222-230. 10.1046/j.1600-6143.2003.00325.xCrossRefPubMed Opelz G, Dohler B: Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004, 4: 222-230. 10.1046/j.1600-6143.2003.00325.xCrossRefPubMed
2.
go back to reference Ghobrial IM, Habermann TM, Macon WR, Ristow KM, Larson TS, Walker RC, Ansell SM, Gores GJ, Stegall MD, McGregor CG: Differences between early and late posttransplant lymphoproliferative disorders in solid organ transplant patients: are they two different diseases? Transplantation 2005, 79: 244-247. 10.1097/01.TP.0000144335.39913.5CCrossRefPubMed Ghobrial IM, Habermann TM, Macon WR, Ristow KM, Larson TS, Walker RC, Ansell SM, Gores GJ, Stegall MD, McGregor CG: Differences between early and late posttransplant lymphoproliferative disorders in solid organ transplant patients: are they two different diseases? Transplantation 2005, 79: 244-247. 10.1097/01.TP.0000144335.39913.5CCrossRefPubMed
3.
go back to reference Bakker NA, van Imhoff GW, Verschuuren EAM, van Son WJ: Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transplant Int 2007, 20: 207-218. 10.1111/j.1432-2277.2006.00416.xCrossRef Bakker NA, van Imhoff GW, Verschuuren EAM, van Son WJ: Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transplant Int 2007, 20: 207-218. 10.1111/j.1432-2277.2006.00416.xCrossRef
4.
go back to reference Nalesnik MA: Clinicopathologic characteristics of post-transplant lymphoproliferative disorders. Recent Results Cancer Res 2002, 159: 9-18. 10.1007/978-3-642-56352-2_2CrossRefPubMed Nalesnik MA: Clinicopathologic characteristics of post-transplant lymphoproliferative disorders. Recent Results Cancer Res 2002, 159: 9-18. 10.1007/978-3-642-56352-2_2CrossRefPubMed
5.
go back to reference Leblond V, Davi F, Charlotte F, Dorent R, Bitker MO, Sutton L, Gandjbakhch I, Binet JL, Raphael M: Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity? J Clin Oncol 1998, 16: 2052-2059.PubMed Leblond V, Davi F, Charlotte F, Dorent R, Bitker MO, Sutton L, Gandjbakhch I, Binet JL, Raphael M: Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity? J Clin Oncol 1998, 16: 2052-2059.PubMed
6.
go back to reference Dotti G, Fiocchi R, Motta T, Mammana C, Gotti E, Riva S, Cornelli P, Gridelli B, Viero P, Oldani E, Ferrazzi P, Remuzzi G, Barbui T, Rambaldi A: Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation 2002, 74: 1095-1102. 10.1097/00007890-200210270-00007CrossRefPubMed Dotti G, Fiocchi R, Motta T, Mammana C, Gotti E, Riva S, Cornelli P, Gridelli B, Viero P, Oldani E, Ferrazzi P, Remuzzi G, Barbui T, Rambaldi A: Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation 2002, 74: 1095-1102. 10.1097/00007890-200210270-00007CrossRefPubMed
7.
go back to reference Lucioni M, Capello D, Riboni R, Ippoliti G, Campana C, Bandiera L, Arcaini L, Rossi D, Cerri M, Dionigi P, Lazzarino M, Magrini U, Viganò M, Gaidano G, Paulli M: B-cell posttransplant lymphoproliferative disorders in heart and/or lung recipients: clinical and molecular-histogenetic study of 17 cases from a single institution. Transplantation 2006, 82: 1013-1023.CrossRefPubMed Lucioni M, Capello D, Riboni R, Ippoliti G, Campana C, Bandiera L, Arcaini L, Rossi D, Cerri M, Dionigi P, Lazzarino M, Magrini U, Viganò M, Gaidano G, Paulli M: B-cell posttransplant lymphoproliferative disorders in heart and/or lung recipients: clinical and molecular-histogenetic study of 17 cases from a single institution. Transplantation 2006, 82: 1013-1023.CrossRefPubMed
8.
go back to reference Schubert S, Renner C, Hammer M, Abdul-Khaliq H, Lehmkuhl HB, Felix Berger F, Hetzer R, Reinke P: Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients. J Heart Lung Transplant 2008, 27: 100-105. 10.1016/j.healun.2007.09.027CrossRefPubMed Schubert S, Renner C, Hammer M, Abdul-Khaliq H, Lehmkuhl HB, Felix Berger F, Hetzer R, Reinke P: Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients. J Heart Lung Transplant 2008, 27: 100-105. 10.1016/j.healun.2007.09.027CrossRefPubMed
9.
go back to reference Baldanti F, Grossi P, Furione M, Simoncini L, Sarasini A, Comoli P, Maccario R, Fiocchi R, Gerna G: High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders. J Clin Microbiol 2000, 38: 613-619.PubMedCentralPubMed Baldanti F, Grossi P, Furione M, Simoncini L, Sarasini A, Comoli P, Maccario R, Fiocchi R, Gerna G: High levels of Epstein-Barr virus DNA in blood of solid-organ transplant recipients and their value in predicting posttransplant lymphoproliferative disorders. J Clin Microbiol 2000, 38: 613-619.PubMedCentralPubMed
10.
go back to reference Stevens SJ, Pronk I, Middeldorp JM: Toward standardization of Epstein-Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen. J Clin Microbiol 2001, 39: 1211-1216. 10.1128/JCM.39.4.1211-1216.2001PubMedCentralCrossRefPubMed Stevens SJ, Pronk I, Middeldorp JM: Toward standardization of Epstein-Barr virus DNA load monitoring: unfractionated whole blood as preferred clinical specimen. J Clin Microbiol 2001, 39: 1211-1216. 10.1128/JCM.39.4.1211-1216.2001PubMedCentralCrossRefPubMed
11.
go back to reference Wagner HJ, Wessel M, Jabs W, Smets F, Fischer L, Offner G, Bucsky P: Patients at risk for development of posttransplant lymphoproliferative disorder: plasma versus peripheral blood mononuclear cells as material for quantification of Epstein-Barr viral load by using real-time quantitative polymerase chain reaction. Transplantation 2001, 72: 1012-1019. 10.1097/00007890-200109270-00006CrossRefPubMed Wagner HJ, Wessel M, Jabs W, Smets F, Fischer L, Offner G, Bucsky P: Patients at risk for development of posttransplant lymphoproliferative disorder: plasma versus peripheral blood mononuclear cells as material for quantification of Epstein-Barr viral load by using real-time quantitative polymerase chain reaction. Transplantation 2001, 72: 1012-1019. 10.1097/00007890-200109270-00006CrossRefPubMed
12.
go back to reference Fafi-Kremer S, Brengel-Pesce K, Barguès G, Bourgeat MJ, Genoulaz O, Seigneurin JM, Morand P: Assessment of automated DNA extraction coupled with realtime PCR for measuring Epstein-Barr virus load in whole blood, peripheral mononuclear cells and plasma. J Clin Virol 2004, 30: 157-164. 10.1016/j.jcv.2003.10.002CrossRefPubMed Fafi-Kremer S, Brengel-Pesce K, Barguès G, Bourgeat MJ, Genoulaz O, Seigneurin JM, Morand P: Assessment of automated DNA extraction coupled with realtime PCR for measuring Epstein-Barr virus load in whole blood, peripheral mononuclear cells and plasma. J Clin Virol 2004, 30: 157-164. 10.1016/j.jcv.2003.10.002CrossRefPubMed
13.
go back to reference Benden C, Aurora P, Burch M, Cubitt D, Lloyd C, Whitmore P, Neligan SL, Elliott MJ: Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction. J Heart Lung Transplant 2005, 24: 2103-2108. 10.1016/j.healun.2005.06.014CrossRefPubMed Benden C, Aurora P, Burch M, Cubitt D, Lloyd C, Whitmore P, Neligan SL, Elliott MJ: Monitoring of Epstein-Barr viral load in pediatric heart and lung transplant recipients by real-time polymerase chain reaction. J Heart Lung Transplant 2005, 24: 2103-2108. 10.1016/j.healun.2005.06.014CrossRefPubMed
14.
go back to reference McDiarmid SV, Jordan S, Kim GS, Toyoda M, Goss JA, Vargas JH, Martín MG, Bahar R, Maxfield AL, Ament ME, Busuttil RW: Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients. Transplantation 1998, 66: 1604-1611. 10.1097/00007890-199812270-00006CrossRefPubMed McDiarmid SV, Jordan S, Kim GS, Toyoda M, Goss JA, Vargas JH, Martín MG, Bahar R, Maxfield AL, Ament ME, Busuttil RW: Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients. Transplantation 1998, 66: 1604-1611. 10.1097/00007890-199812270-00006CrossRefPubMed
15.
go back to reference Comoli P, Labirio M, Basso S, Baldanti F, Grossi P, Furione M, Viganò M, Fiocchi R, Rossi G, Ginevri F, Gridelli B, Moretta A, Montagna D, Locatelli F, Gerna G, Maccario R: Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 2002, 99: 2592-2598. 10.1182/blood.V99.7.2592CrossRefPubMed Comoli P, Labirio M, Basso S, Baldanti F, Grossi P, Furione M, Viganò M, Fiocchi R, Rossi G, Ginevri F, Gridelli B, Moretta A, Montagna D, Locatelli F, Gerna G, Maccario R: Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 2002, 99: 2592-2598. 10.1182/blood.V99.7.2592CrossRefPubMed
16.
go back to reference Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y, Barshes NR, Scott JD, Bristow LJ, O'Mahony CA, Goss JA: Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant 2005, 5: 2222-2228. 10.1111/j.1600-6143.2005.01002.xCrossRefPubMed Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y, Barshes NR, Scott JD, Bristow LJ, O'Mahony CA, Goss JA: Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant 2005, 5: 2222-2228. 10.1111/j.1600-6143.2005.01002.xCrossRefPubMed
17.
go back to reference Baldanti F, Gatti M, Furione M, Paolucci S, Tinelli C, Comoli P, Merli P, Locatelli F: Kinetics of Epstein-Barr virus DNA load in different blood compartments of pediatric recipients of T-cell-depleted HLA-haploidentical stem cell transplantation. J Clin Microbiol 2008, 46: 3672-3677. 10.1128/JCM.00913-08PubMedCentralCrossRefPubMed Baldanti F, Gatti M, Furione M, Paolucci S, Tinelli C, Comoli P, Merli P, Locatelli F: Kinetics of Epstein-Barr virus DNA load in different blood compartments of pediatric recipients of T-cell-depleted HLA-haploidentical stem cell transplantation. J Clin Microbiol 2008, 46: 3672-3677. 10.1128/JCM.00913-08PubMedCentralCrossRefPubMed
18.
go back to reference Raj R, Frost AE: Lung retransplantation after posttransplantantation lymphoproliferative disorder (PTLD): a single-center experience and review of literature of PTLD in lung transplant recipients. J Heart Lung Transplant 2005, 24: 671-679. 10.1016/j.healun.2004.04.011CrossRefPubMed Raj R, Frost AE: Lung retransplantation after posttransplantantation lymphoproliferative disorder (PTLD): a single-center experience and review of literature of PTLD in lung transplant recipients. J Heart Lung Transplant 2005, 24: 671-679. 10.1016/j.healun.2004.04.011CrossRefPubMed
19.
go back to reference Levenson BM, Ali SA, Timmons CF, Mittal N, Muthukumar A, Payne DA: Unusual case of Epstein-Barr virus DNA tissue positive: Blood negative in a patient with post-transplant lymphoproliferative disorder. Pediatr Transplantation 2009, 13: 134-138. 10.1111/j.1399-3046.2008.00965.xCrossRef Levenson BM, Ali SA, Timmons CF, Mittal N, Muthukumar A, Payne DA: Unusual case of Epstein-Barr virus DNA tissue positive: Blood negative in a patient with post-transplant lymphoproliferative disorder. Pediatr Transplantation 2009, 13: 134-138. 10.1111/j.1399-3046.2008.00965.xCrossRef
Metadata
Title
Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a cohort of lung transplant recipients
Authors
Fausto Baldanti
Vanina Rognoni
Alessandro Cascina
Tiberio Oggionni
Carmine Tinelli
Federica Meloni
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2011
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-8-421

Other articles of this Issue 1/2011

Virology Journal 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine