Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients

Clinical Microbiology and Infection

Volumn 20, Issue s7, 2014, Pages 109-118

  San Juan, R ^a   Comoli, P ^b   Caillard, S ^c   Moulin, B ^c   Hirsch, H H ^d,e   Meylan, P ^f  

^a Universidad Complutense   (Spain)

^b FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^c UNIVERSITY HOSPITAL OF STRASBOURG   (France)

^d UNIVERSITY OF BASEL   (Switzerland)

^e UNIVERSITY HOSPITAL BASEL   (Switzerland)

^f LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

Epstein Barr virus; Post transplant lymphoproliferative disease; Recommendations; Risk factors; Viral kinetics

Indexed keywords

ANTIVIRUS AGENT; RITUXIMAB; IMMUNOSUPPRESSIVE AGENT;

DISEASE REGISTRY; EPIDEMIOLOGICAL DATA; EPSTEIN BARR VIRUS; EPSTEIN BARR VIRUS INFECTION; FOLLOW UP; GRAFT RECIPIENT; HIGH RISK POPULATION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; INCIDENCE; ORGAN TRANSPLANTATION; PATHOGENESIS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; REVIEW; RISK FACTOR; SOLID ORGAN TRANSPLANT; T LYMPHOCYTE; TREATMENT DURATION; EPIDEMIOLOGICAL MONITORING; EPSTEIN-BARR VIRUS INFECTIONS; IMMUNOCOMPROMISED PATIENT; LYMPHOPROLIFERATIVE DISORDERS; MASS SCREENING; MOLECULAR DIAGNOSIS; OPPORTUNISTIC INFECTIONS; PROCEDURES;

EPIDEMIOLOGICAL MONITORING; EPSTEIN-BARR VIRUS INFECTIONS; HUMANS; IMMUNOCOMPROMISED HOST; IMMUNOSUPPRESSIVE AGENTS; LYMPHOPROLIFERATIVE DISORDERS; MASS SCREENING; MOLECULAR DIAGNOSTIC TECHNIQUES; OPPORTUNISTIC INFECTIONS; ORGAN TRANSPLANTATION; TRANSPLANT RECIPIENTS;

EID: 84908154325     PISSN: 1198743X     EISSN: 14690691     Source Type: Journal    
DOI: 10.1111/1469-0691.12534     Document Type: Review

References (90)

1. Knight JS, Tsodikov A, Cibrik DM, Ross CW, Kaminski MS, Blayney DW. Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation centre. J Clin Oncol 2009; 27: 3354-3362.
2. Dharnidharka VR, Lamb KE, Gregg JA, Meier-Kriesche HU. Associations between EBV serostatus and organ transplant type in PTLD risk: an analysis of the SRTR national registry data in the United States. Am J Transplant 2012; 12: 976-983.
3. Burns DM, Crawford DH. Epstein-Barr virus-specific cytotoxic T-lymphocytes for adoptive immunotherapy of post-transplant lymphoproliferative disease. Blood Rev 2004; 18: 193-209.
4. Green M, Michaels MG. Epstein-Barr virus infection and post-transplant lymphoproliferative disorder. Am J Transplant 2013; 13 (suppl 3): 41-54.
5. Caillard S, Lelong C, Pessione F, Moulin B. Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French registry. Am J Transplant 2006; 6: 2735-2742.
6. Parker A, Bowles K, Bradley JA et al. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS guidelines. Br J Haematol 2010; 149: 675-692.
7. Allen U, Hebert D, Moore D, Dror Y, Wasfy S. Epstein-Barr virus-related post-transplant lymphoproliferative disease in solid organ transplant recipients, 1988-97: a Canadian multi-centre experience. Pediatr Transplant 2001; 5: 198-203.
8. Hoshida Y, Li T, Dong Z et al. Lymphoproliferative disorders in renal transplant patients in Japan. Int J Cancer 2001; 91: 869-875.
9. Reddy N, Rezvani K, Barrett AJ, Savani BN. Strategies to prevent EBV reactivation and post-transplant lymphoproliferative disorders (PTLD) after allogeneic stem cell transplantation in high-risk patients. Biol Blood Marrow Transplant 2011; 17: 591-597.
10. Parker A, Bowles K, Bradley JA et al. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients - BCSH and BTS guidelines. Br J Haematol 2010; 149: 693-705.
11. Glotz D, Chapman JR, Dharnidharka VR et al. The Seville expert workshop for progress in post-transplant lymphoproliferative disorders. Transplantation 2012; 94: 784-793.
12. Kish MA. Guide to development of practice guidelines. Clin Infect Dis 2001; 32: 851-854.
13. Dharnidharka VR, Tejani AH, Ho PL, Harmon WE. Post-transplant lymphoproliferative disorder in the United States: young Caucasian males are at highest risk. Am J Transplant 2002; 2: 993-998.
14. Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993; 342: 1514-1516.
15. Sampaio MS, Cho YW, Qazi Y, Bunnapradist S, Hutchinson IV, Shah T. Post-transplant malignancies in solid organ adult recipients: an analysis of the U.S. National Transplant Database. Transplantation 2012; 94: 990-998.
16. Caillard S, Lamy FX, Quelen C et al. Epidemiology of post-transplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. Am J Transplant 2012; 12: 682-693.
17. Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant 2004; 4: 222-230.
18. Collett D, Mumford L, Banner NR, Neuberger J, Watson C. Comparison of the incidence of malignancy in recipients of different types of organ: a UK registry audit. Am J Transplant 2010; 10: 1889-1896.
19. Dharnidharka VR, Sullivan EK, Stablein DM, Tejani AH, Harmon WE. Risk factors for post-transplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American pediatric renal transplant cooperative study (NAPRTCS). Transplantation 2001; 71: 1065-1068.
20. Fernberg P, Edgren G, Adami J et al. Time trends in risk and risk determinants of non-Hodgkin lymphoma in solid organ transplant recipients. Am J Transplant 2011; 11: 2472-2482.
21. Sampaio MS, Cho YW, Shah T, Bunnapradist S, Hutchinson IV. Impact of Epstein-Barr virus donor and recipient serostatus on the incidence of post-transplant lymphoproliferative disorder in kidney transplant recipients. Nephrol Dial Transplant 2012; 27: 2971-2979.
22. van Leeuwen MT, Grulich AE, Webster AC et al. Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation. Blood 2009; 114: 630-637.
23. Quinlan SC, Pfeiffer RM, Morton LM, Engels EA. Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States. Am J Hematol 2011; 86: 206-209.
24. Birkeland SA, Hamilton-Dutoit S. Is post-transplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se? Transplantation 2003; 76: 984-988.
25. Duvoux C, Pageaux GP, Vanlemmens C et al. Risk factors for lymphoproliferative disorders after liver transplantation in adults: an analysis of 480 patients. Transplantation 2002; 74: 1103-1109.
26. Bakker NA, van Imhoff GW, Verschuuren EA et al. HLA antigens and post renal transplant lymphoproliferative disease: HLA-b matching is critical. Transplantation 2005; 80: 595-599.
27. Cherikh WS, Kauffman HM, McBride MA, Maghirang J, Swinnen LJ, Hanto DW. Association of the type of induction immunosuppression with post-transplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 2003; 76: 1289-1293.
28. Faull RJ, Hollett P, McDonald SP. Lymphoproliferative disease after renal transplantation in Australia and New Zealand. Transplantation 2005; 80: 193-197.
29. Bustami RT, Ojo AO, Wolfe RA et al. Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients. Am J Transplant 2004; 4: 87-93.
30. Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Post-transplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation 2005; 80: 1233-1243.
31. Kirk AD, Cherikh WS, Ring M et al. Dissociation of depletional induction and post-transplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. Am J Transplant 2007; 7: 2619-2625.
32. Younes BS, McDiarmid SV, Martin MG et al. The effect of immunosuppression on post-transplant lymphoproliferative disease in pediatric liver transplant patients. Transplantation 2000; 70: 94-99.
33. Dharnidharka VR, Ho PL, Stablein DM, Harmon WE, Tejani AH. Mycophenolate, tacrolimus and post-transplant lymphoproliferative disorder: a report of the North American pediatric renal transplant cooperative study. Pediatr Transplant 2002; 6: 396-399.
34. Sampaio MS, Cho YW, Shah T, Bunnapradist S, Hutchinson IV. Association of immunosuppressive maintenance regimens with post-transplant lymphoproliferative disorder in kidney transplant recipients. Transplantation 2012; 93: 73-81.
35. Robson R, Cecka JM, Opelz G, Budde M, Sacks S. Prospective registry-based observational cohort study of the long-term risk of malignancies in renal transplant patients treated with mycophenolate mofetil. Am J Transplant 2005; 5: 2954-2960.
36. Funch DP, Ko HH, Travasso J et al. Post-transplant lymphoproliferative disorder among renal transplant patients in relation to the use of mycophenolate mofetil. Transplantation 2005; 80: 1174-1180.
37. Hocker B, Bohm S, Fickenscher H et al. (Val-)Ganciclovir prophylaxis reduces Epstein-Barr virus primary infection in pediatric renal transplantation. Transpl Int 2012; 25: 723-731.
38. Hocker B, Fickenscher H, Delecluse HJ et al. Epidemiology and morbidity of Epstein-Barr virus infection in pediatric renal transplant recipients: a multicenter, prospective study. Clin Infect Dis 2013; 56: 84-92.
39. McDonald RA, Smith JM, Ho M et al. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant 2008; 8: 984-989.
40. Opelz G, Daniel V, Naujokat C, Fickenscher H, Dohler B. Effect of cytomegalovirus prophylaxis with immunoglobulin or with antiviral drugs on post-transplant non-Hodgkin lymphoma: a multicentre retrospective analysis. Lancet Oncol 2007; 8: 212-218.
41. Green M, Michaels MG, Katz BZ et al. CMV-IVIG for prevention of Epstein Barr virus disease and post-transplant lymphoproliferative disease in pediatric liver transplant recipients. Am J Transplant 2006; 6: 1906-1912.
42. Funch DP, Walker AM, Schneider G, Ziyadeh NJ, Pescovitz MD. Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients. Am J Transplant 2005; 5: 2894-2900.
43. Meng Q, Hagemeier SR, Fingeroth JD, Gershburg E, Pagano JS, Kenney SC. The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production. J Virol 2010; 84: 4534-4542.
44. Funk GA, Gosert R, Hirsch HH. Viral dynamics in transplant patients: implications for disease. Lancet Infect Dis 2007; 7: 460-472.
45. Hong GK, Gulley ML, Feng WH, Delecluse HJ, Holley-Guthrie E, Kenney SC. Epstein-Barr virus lytic infection contributes to lymphoproliferative disease in a SCID mouse model. J Virol 2005; 79: 13993-14003.
46. Thorley-Lawson DA, Gross A. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N Engl J Med 2004; 350: 1328-1337.
47. Cockfield SM. Identifying the patient at risk for post-transplant lymphoproliferative disorder. Transpl Infect Dis 2001; 3: 70-78.
48. Jabs WJ, Hennig H, Kittel M et al. Normalized quantification by real-time PCR of Epstein-Barr virus load in patients at risk for post-transplant lymphoproliferative disorders. J Clin Microbiol 2001; 39: 564-569.
49. Gartner B, Preiksaitis JK. EBV viral load detection in clinical virology. J Clin Virol 2010; 48: 82-90.
50. Allen UD, Preiksaitis JK. Epstein-Barr virus and post-transplant lymphoproliferative disorder in solid organ transplantation. Am J Transplant 2013; 13(suppl 4): 107-120.
51. Wagner HJ, Wessel M, Jabs W et al. Patients at risk for development of post-transplant 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.
52. Wagner HJ, Fischer L, Jabs WJ, Holbe M, Pethig K, Bucsky P. Longitudinal analysis of Epstein-Barr viral load in plasma and peripheral blood mononuclear cells of transplanted patients by real-time polymerase chain reaction. Transplantation 2002; 74: 656-664.
53. Preiksaitis JK, Pang XL, Fox JD, Fenton JM, Caliendo AM, Miller GG. Interlaboratory comparison of Epstein-Barr virus viral load assays. Am J Transplant 2009; 9: 269-279.
54. Rowe DT, Webber S, Schauer EM, Reyes J, Green M. Epstein-Barr virus load monitoring: its role in the prevention and management of post-transplant lymphoproliferative disease. Transpl Infect Dis 2001; 3: 79-87.
55. San-Juan R, De Dios B, Navarro D et al. Epstein-Barr virus DNAemia is an early surrogate marker of the net state of immunosuppresion in solid organ transplant recipients. Transplantation 2013; 95: 688-693.
56. Holmes MV, Caplin B, Atkinson C et al. Prospective monitoring of Epstein-Barr virus DNA in adult renal transplant recipients during the early post-transplant period: role of mycophenolate mofetil. Transplantation 2009; 87: 852-856.
57. Bamoulid J, Courivaud C, Coaquette A et al. Subclinical Epstein-Barr virus viremia among adult renal transplant recipients: incidence and consequences. Am J Transplant 2013; 13: 656-662.
58. Bakker NA, Verschuuren EA, Erasmus ME et al. Epstein-Barr virus-DNA load monitoring late after lung transplantation: a surrogate marker of the degree of immunosuppression and a safe guide to reduce immunosuppression. Transplantation 2007; 83: 433-438.
59. Gotoh K, Ito Y, Ohta R et al. Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads. J Infect Dis 2010; 202: 461-469.
60. Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355: 2032-2036.
61. Smets F, Latinne D, Bazin H et al. Ratio between Epstein-Barr viral load and anti- Epstein-Barr virus specific T-cell response as a predictive marker of post-transplant lymphoproliferative disease. Transplantation 2002; 73: 1603-1610.
62. Schubert S, Renner C, Hammer M et al. Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients. J Heart Lung Transplant 2008; 27: 100-105.
63. Toyoda M, Moudgil A, Warady BA, Puliyanda DP, Jordan SC. Clinical significance of peripheral blood Epstein-Barr viral load monitoring using polymerase chain reaction in renal transplant recipients. Pediatr Transplant 2008; 12: 778-784.
64. Gulley ML, Tang W. Using Epstein-Barr viral load assays to diagnose, monitor, and prevent post-transplant lymphoproliferative disorder. Clin Microbiol Rev 2010; 23: 350-366.
65. Martin SI, Dodson B, Wheeler C, Davis J, Pesavento T, Bumgardner GL. Monitoring infection with Epstein-Barr virus among seromismatch adult renal transplant recipients. Am J Transplant 2011; 2011: 1600-6143.
66. Lee TC, Savoldo B, Rooney CM et al. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant 2005; 5: 2222-2228.
67. D'Antiga L, Del Rizzo M, Mengoli C, Cillo U, Guariso G, Zancan L. Sustained Epstein-Barr virus detection in paediatric liver transplantation. Insights into the occurrence of late PTLD. Liver Transpl 2007; 13: 343-348.
68. Green M. Management of Epstein-Barr virus-induced post-transplant lymphoproliferative disease in recipients of solid organ transplantation. Am J Transplant 2001; 1: 103-108.
69. Tsai DE, Douglas L, Andreadis C et al. EBV PCR in the diagnosis and monitoring of post-transplant lymphoproliferative disorder: results of a two-arm prospective trial. Am J Transplant 2008; 8: 1016-1024.
70. Evens AM, David KA, Helenowski I et al. Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era. J Clin Oncol 2010; 28: 1038-1046.
71. Bakker NA, Pruim J, de Graaf W, van Son WJ, van der Jagt EJ, van Imhoff GW. PTLD visualization by FDG-pet: improved detection of extranodal localizations. Am J Transplant 2006; 6: 1984-1985.
72. McDiarmid SV, Jordan S, Kim GS et al. Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients. Transplantation 1998; 66: 1604-1611.
73. Ginevri F, Di Marco E, Parodi A et al. EBV viral load monitoring and reduction of immunosuppression do not successfully prevent PTLD after pediatric kidney transplantation. Am J Transplant 2008; 8(suppl 2): 477.
74. Furukawa S, Wei L, Krams SM, Esquivel CO, Martinez OM. Pi3Kδ inhibition augments the efficacy of rapamycin in suppressing proliferation of Epstein-Barr virus (EBV)+ B cell lymphomas. Am J Transplant 2013; 13: 2035-2043.
75. Vaysberg M, Balatoni CE, Nepomuceno RR, Krams SM, Martinez OM. Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas through modulation of cell-cycle protein expression. Transplantation 2007; 83: 1114-1121.
76. Cullis B, D'Souza R, McCullagh P et al. Sirolimus-induced remission of post-transplantation lymphoproliferative disorder. Am J Kidney Dis 2006; 47: e67-e72.
77. Sampaio MS, Cho YW, Shah T, Bunnapradist S, Hutchinson IV. Association of immunosuppressive maintenance regimens with post-transplant lymphoproliferative disorder in kidney transplant recipients. Transplantation 2011; 93: 73-81.
78. Hierro L, Diez-Dorado R, Diaz C et al. Efficacy and safety of valganciclovir in liver-transplanted children infected with Epstein-Barr virus. Liver Transpl 2008; 14: 1185-1193.
79. Venturi C, Bueno J, Gavalda J et al. Impact of valganciclovir on Epstein-Barr virus polymerase chain reaction in pediatric liver transplantation: preliminary report. Transplant Proc 2009; 41: 1038-1040.
80. Choquet S, Leblond V, Herbrecht R et al. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood 2006; 107: 3053-3057.
81. Trappe R, Oertel S, Leblond V et al. Sequential treatment with rituximab followed by chop chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial. Lancet Oncol 2012; 13: 196-206.
82. van Esser JW, Niesters HG, van der Holt B et al. Prevention of Epstein-Barr virus-lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood 2002; 99: 4364-4369.
83. Comoli P, Basso S, Zecca M et al. Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am J Transplant 2007; 7: 1648-1655.
84. Choquet S, Oertel S, LeBlond V et al. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution. Ann Hematol 2007; 86: 599-607.
85. Bollard CM, Rooney CM, Heslop HE. T-cell therapy in the treatment of post-transplant lymphoproliferative disease. Nat Rev Clin Oncol 2012; 9: 510-519.
86. Comoli P, Labirio M, Basso S et al. 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.
87. Savoldo B, Goss JA, Hammer MM et al. Treatment of solid organ transplant recipients with autologous Epstein-Barr virus-specific cytotoxic T lymphocytes (CTLS). Blood 2006; 108: 2942-2949.
88. Haque T, Wilkie GM, Jones MM et al. Allogeneic cytotoxic T-cell therapy for EBV-positive post-transplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood 2007; 110: 1123-1131.
89. Davis CL, Wood BL, Sabath DE, Joseph JS, Stehman-Breen C, Broudy VC. Interferon-alpha treatment of post-transplant lymphoproliferative disorder in recipients of solid organ transplants. Transplantation 1998; 66: 1770-1779.
90. Haddad E, Paczesny S, Leblond V et al. Treatment of b-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial. Blood 2001; 97: 1590-1597.