Diagnostic Considerations

Posttransplant lymphoproliferative disease (PTLD) can present in a wide variety of ways. The differential diagnosis should include any condition that would be on the differential diagnosis appropriate for those particular symptoms in any patient. Patients who are immunosuppressed, in addition to being at risk for lymphoproliferative disease or opportunistic infections, are also at risk for the same conditions as patients who are immunocompetent. For example, if a patient who is immunosuppressed presents with fever, pharyngitis, and cervical lymphadenopathy, the differential diagnosis might include streptococcal infection and infectious mononucleosis, as well as PTLD.

Workup

Dharnidharka VR. Comprehensive review of post-organ transplant hematologic cancers. Am J Transplant. 2018 Mar. 18 (3):537-549. [QxMD MEDLINE Link].
Glotz D, Chapman JR, Dharnidharka VR, Hanto DW, Castro MC, Hirsch HH, et al. The Seville Expert Workshop for Progress in Posttransplant Lymphoproliferative Disorders. Transplantation. 2012 Sep 18. [QxMD MEDLINE Link].
Post-transplant lymphoproliferative disorders (PTLD). Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, eds. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Lyon, France: IARC; 2016. 452-464.
Bakker NA, van Imhoff GW. Post-transplant lymphoproliferative disorders: from treatment to early detection and prevention?. Haematologica. 2007 Nov. 92(11):1447-50. [QxMD MEDLINE Link].
Capello D, Berra E, Cerri M, Gaidano G. Post-transplant lymphoproliferative disorders. Molecular analysis of histogenesis and pathogenesis. Minerva Med. 2004 Feb. 95(1):53-64. [QxMD MEDLINE Link].
Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000 Aug 17. 343(7):481-92. [QxMD MEDLINE Link].
Henle G, Henle W, Diehl V. Relation of Burkitt's tumor-associated herpes-type virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan. 59(1):94-101. [QxMD MEDLINE Link].
Cen H, Williams PA, McWilliams HP, et al. Evidence for restricted Epstein-Barr virus latent gene expression and anti-EBNA antibody response in solid organ transplant recipients with posttransplant lymphoproliferative disorders. Blood. 1993 Mar 1. 81(5):1393-403. [QxMD MEDLINE Link].
Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964. 1:702-3.
Greenspan JS, Greenspan D, Lennette ET. Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion. N Engl J Med. 1985 Dec 19. 313(25):1564-71. [QxMD MEDLINE Link].
zur Hausen H, Schulte-Holthausen H, Klein G, et al. EBV DNA in biopsies of Burkitt tumours and anaplastic carcinomas of the nasopharynx. Nature. 1970 Dec 12. 228(276):1056-8. [QxMD MEDLINE Link].
Shaknovich R, Basso K, Bhagat G, et al. Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling. Haematologica. 2006 Oct. 91(10):1313-20. [QxMD MEDLINE Link].
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 Mar. 13(3):343-8. [QxMD MEDLINE Link].
Vietzen H, Furlano PL, Cornelissen JJ, Böhmig GA, Jaksch P, Puchhammer-Stöckl E. HLA-E-restricted immune responses are crucial for the control of EBV infections and the prevention of PTLD. Blood. 2023 Mar 30. 141 (13):1560-1573. [QxMD MEDLINE Link]. [Full Text].
Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R. An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation. 1995 Feb 27. 59(4):524-9. [QxMD MEDLINE Link].
Swinnen LJ, LeBlanc M, Grogan TM, Gordon LI, Stiff PJ, Miller AM. Prospective study of sequential reduction in immunosuppression, interferon alpha-2B, and chemotherapy for posttransplantation lymphoproliferative disorder. Transplantation. 2008 Jul 27. 86(2):215-22. [QxMD MEDLINE Link].
Ziegler JL, Drew WL, Miner RC, et al. Outbreak of Burkitt's-like lymphoma in homosexual men. Lancet. 1982 Sep 18. 2(8299):631-3. [QxMD MEDLINE Link].
Schubert S, Renner C, Hammer M, Abdul-Khaliq H, Lehmkuhl HB, Berger F. Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients. J Heart Lung Transplant. 2008 Jan. 27(1):100-5. [QxMD MEDLINE Link].
Knowles DM, Cesarman E, Chadburn A. Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood. 1995 Jan 15. 85(2):552-65. [QxMD MEDLINE Link].
LaCasce AS. Post-transplant lymphoproliferative disorders. Oncologist. 2006 Jun. 11(6):674-80. [QxMD MEDLINE Link].
Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2004 Aug 11.
Caillard S, Lamy FX, Quelen C, Dantal J, Lebranchu Y, Lang P. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. Am J Transplant. 2012 Mar. 12(3):682-93. [QxMD MEDLINE Link].
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 Apr. 12(4):976-83. [QxMD MEDLINE Link].
Jamali FR, Otrock ZK, Soweid AM, Al-Awar GN, Mahfouz RA, Haidar GR. An overview of the pathogenesis and natural history of post-transplant T-cell lymphoma. Leuk Lymphoma. 2007 Jun. 48(6):1237-41. [QxMD MEDLINE Link].
Green M, Webber S. Posttransplantation lymphoproliferative disorders. Pediatr Clin North Am. 2003 Dec. 50(6):1471-91. [QxMD MEDLINE Link].
Ghobrial I, Habermann T, Ristow K, et al. Prognostic factors in patients with post-transplant lymphoproliferative disorders (PTLD) in the rituximab era. Leuk Lymphoma. 2005 Feb. 46(2):191-6. [QxMD MEDLINE Link].
Liu M, Husain S, Famure O, Li Y, Kim SJ. Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients. Prog Transplant. 2019 Jun. 29 (2):185-193. [QxMD MEDLINE Link].
Sampaio MS, Cho YW, Qazi Y, Bunnapradist S, Hutchinson IV, Shah T. Posttransplant malignancies in solid organ adult recipients: an analysis of the U.S. National Transplant Database. Transplantation. 2012 Nov 27. 94(10):990-8. [QxMD MEDLINE Link].
McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008 May. 8(5):984-9. [QxMD MEDLINE Link].
Cleper R, Ben Shalom E, Landau D, Weissman I, Krause I, Konen O. Post-transplantation lymphoproliferative disorder in pediatric kidney-transplant recipients - a national study. Pediatr Transplant. 2012 Sep. 16(6):619-26. [QxMD MEDLINE Link].
Draoua HY, Tsao L, Mancini DM, et al. T-cell post-transplantation lymphoproliferative disorders after cardiac transplantation: a single institutional experience. Br J Haematol. 2004 Nov. 127(4):429-32. [QxMD MEDLINE Link].
Kremers WK, Devarbhavi HC, Wiesner RH, Krom RA, Macon WR, Habermann TM. Post-transplant lymphoproliferative disorders following liver transplantation: incidence, risk factors and survival. Am J Transplant. 2006 May. 6(5 Pt 1):1017-24. [QxMD MEDLINE Link].
Zimmermann T, Hoppe-Lotichius M, Tripkovic V, Barreiros AP, Wehler TC, Zimmermann A, et al. Liver transplanted patients with preoperative autoimmune hepatitis and immunological disorders are at increased risk for Post-Transplant Lymphoproliferative Disease (PTLD). Eur J Intern Med. 2010 Jun. 21(3):208-15. [QxMD MEDLINE Link].
Hartmann C, Schuchmann M, Zimmermann T. Posttransplant lymphoproliferative disease in liver transplant patients. Curr Infect Dis Rep. 2011 Feb. 13(1):53-9. [QxMD MEDLINE Link].
Cao S, Cox KL, Berquist W, Hayashi M, Concepcion W, Hammes GB. Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus. Pediatr Transplant. 1999 Feb. 3(1):22-6. [QxMD MEDLINE Link].
Kremer BE, Reshef R, Misleh JG, Christie JD, Ahya VN, Blumenthal NP. Post-transplant lymphoproliferative disorder after lung transplantation: a review of 35 cases. J Heart Lung Transplant. 2012 Mar. 31(3):296-304. [QxMD MEDLINE Link].
Jagadeesh D, Woda BA, Draper J, Evens AM. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr Treat Options Oncol. 2012 Mar. 13(1):122-36. [QxMD MEDLINE Link].
Hauke R, Smir B, Greiner T. Clinical and pathological features of posttransplant lymphoproliferative disorders: influence on survival and response to treatment. Ann Oncol. 2001 Jun. 12(6):831-4. [QxMD MEDLINE Link]. [Full Text].
Leblond V, Dhedin N, Mamzer Bruneel MF, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol. 2001 Feb 1. 19(3):772-8. [QxMD MEDLINE Link].
Balaguer-Rosello A, Piñana JL, Bataller L, Montoro J, Romero S, Navarro I, et al. Central Nervous System Involvement in Epstein-Barr Virus-Related Post-Transplant Lymphoproliferative Disorders after Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2021 Mar. 27 (3):261.e1-261.e7. [QxMD MEDLINE Link].
Meerbach A, Wutzler P, Häfer R, Zintl F, Gruhn B. Monitoring of Epstein-Barr virus load after hematopoietic stem cell transplantation for early intervention in post-transplant lymphoproliferative disease. J Med Virol. 2008 Mar. 80(3):441-54. [QxMD MEDLINE Link].
Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant. 2005 Sep. 5(9):2222-8. [QxMD MEDLINE Link].
Riddler SA, Breinig MC, McKnight JL. Increased levels of circulating Epstein-Barr virus (EBV)-infected lymphocytes and decreased EBV nuclear antigen antibody responses are associated with the development of posttransplant lymphoproliferative disease in solid-organ transplant recipients. Blood. 1994 Aug 1. 84(3):972-84. [QxMD MEDLINE Link].
Buell JF, Gross TG, Hanaway MJ, Trofe J, Muthiak C, First MR. Chemotherapy for posttransplant lymphoproliferative disorder: the Israel Penn International Transplant Tumor Registry experience. Transplant Proc. 2005 Mar. 37(2):956-7. [QxMD MEDLINE Link].
Hanson MN, Morrison VA, Peterson BA, et al. Posttransplant T-cell lymphoproliferative disorders--an aggressive, late complication of solid-organ transplantation. Blood. 1996 Nov 1. 88(9):3626-33. [QxMD MEDLINE Link].
Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, et al. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy. Lancet. 1984 Mar 17. 1 (8377):583-7. [QxMD MEDLINE Link].
Benkerrou M, Durandy A, Fischer A. Therapy for transplant-related lymphoproliferative diseases. Hematol Oncol Clin North Am. 1993 Apr. 7 (2):467-75. [QxMD MEDLINE Link].
Samant H, Vaitla P, Kothadia JP. Post Transplant Lymphoproliferative Disorders. 2020 Jan. [QxMD MEDLINE Link]. [Full Text].
Gordan LN, Grow WB, Pusateri A, Douglas V, Mendenhall NP, Lynch JW. Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol. 2005 Feb 20. 23(6):1096-102. [QxMD MEDLINE Link].
Choquet S, Oertel S, LeBlond V, Riess H, Varoqueaux N, Dörken B. Rituximab in the management of post-transplantation lymphoproliferative disorder after solid organ transplantation: proceed with caution. Ann Hematol. 2007 Aug. 86(8):599-607. [QxMD MEDLINE Link].
Choquet S, Leblond V, Herbrecht R, Socié G, Stoppa AM, Vandenberghe P. Efficacy and safety of rituximab in B-cell post-transplantation lymphoproliferative disorders: results of a prospective multicenter phase 2 study. Blood. 2006 Apr 15. 107(8):3053-7. [QxMD MEDLINE Link].
Trappe R, Oertel S, Leblond V, Mollee P, Sender M, Reinke P. 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 Feb. 13(2):196-206. [QxMD MEDLINE Link].
Zimmermann H, Koenecke C, Dreyling MH, Pott C, Dührsen U, Hahn D, et al. Modified risk-stratified sequential treatment (subcutaneous rituximab with or without chemotherapy) in B-cell Post-transplant lymphoproliferative disorder (PTLD) after Solid organ transplantation (SOT): the prospective multicentre phase II PTLD-2 trial. Leukemia. 2022 Oct. 36 (10):2468-2478. [QxMD MEDLINE Link]. [Full Text].
[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf. Version 5.2022 — July 12, 2022; Accessed: October 8, 2022.
Gross TG, Bucuvalas JC, Park JR, Greiner TC, Hinrich SH, Kaufman SS. Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation. J Clin Oncol. 2005 Sep 20. 23(27):6481-8. [QxMD MEDLINE Link].
Gross TG, Orjuela MA, Perkins SL, Park JR, Lynch JC, Cairo MS, et al. Low-Dose Chemotherapy and Rituximab for Posttransplant Lymphoproliferative Disease (PTLD): A Children's Oncology Group Report. Am J Transplant. 2012 Aug 6. [QxMD MEDLINE Link].
Benkerrou M, Jais JP, Leblond V, et al. Anti-B-cell monoclonal antibody treatment of severe posttransplant B- lymphoproliferative disorder: prognostic factors and long-term outcome. Blood. 1998 Nov 1. 92(9):3137-47. [QxMD MEDLINE Link].
Faro A, Kurland G, Michaels MG, et al. Interferon-alpha affects the immune response in post-transplant lymphoproliferative disorder. Am J Respir Crit Care Med. 1996 Apr. 153(4 Pt 1):1442-7. [QxMD MEDLINE Link].
Shapiro RS, Chauvenet A, McGuire W, et al. Treatment of B-cell lymphoproliferative disorders with interferon alfa and intravenous gamma globulin. N Engl J Med. 1988 May 19. 318(20):1334. [QxMD MEDLINE Link].
O'Brien S, Bernert RA, Logan JL, Lien YH. Remission of posttransplant lymphoproliferative disorder after interferon alfa therapy. J Am Soc Nephrol. 1997 Sep. 8(9):1483-9. [QxMD MEDLINE Link].
Fischer A, Blanche S, Le Bidois J, et al. Anti-B-cell monoclonal antibodies in the treatment of severe B-cell lymphoproliferative syndrome following bone marrow and organ transplantation. N Engl J Med. 1991 May 23. 324(21):1451-6. [QxMD MEDLINE Link].
Milpied N, Vasseur B, Parquet N, et al. Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: a retrospective analysis on 32 patients. Ann Oncol. 2000. 11 Suppl 1:113-6. [QxMD MEDLINE Link].
Papadopoulos EB, Ladanyi M, Emanuel D. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med. 1994 Apr 28. 330(17):1185-91. [QxMD MEDLINE Link].
Cruz RJ Jr, Ramachandra S, Sasatomi E, Dimartini A, de Vera M, Fontes P, et al. Surgical management of gastrointestinal posttransplant lymphoproliferative disorders in liver transplant recipients. Transplantation. 2012 Aug 27. 94(4):417-23. [QxMD MEDLINE Link].
Becker YT, Samaniego-Picota M, Sollinger HW. The emerging role of rituximab in organ transplantation. Transpl Int. 2006 Aug. 19(8):621-8. [QxMD MEDLINE Link].
González-Barca E, Domingo-Domenech E, Capote FJ, Gómez-Codina J, Salar A, Bailen A. Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease. Haematologica. 2007 Nov. 92(11):1489-94. [QxMD MEDLINE Link].
Taj MM, Messahel B, Mycroft J, Pritchard-Jones K, Baker A, Height S. Efficacy and tolerability of high-dose methotrexate in central nervous system positive or relapsed lymphoproliferative disease following liver transplant in children. Br J Haematol. 2008 Jan. 140(2):191-6. [QxMD MEDLINE Link].
Bollard CM, Rooney CM, Heslop HE. T-cell therapy in the treatment of post-transplant lymphoproliferative disease. Nat Rev Clin Oncol. 2012 Sep. 9(9):510-9. [QxMD MEDLINE Link].
Doubrovina E, Oflaz-Sozmen B, Prockop SE, Kernan NA, Abramson S, Teruya-Feldstein J. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012 Mar 15. 119(11):2644-56. [QxMD MEDLINE Link].
Jiang X, Xu L, Zhang Y, Huang F, Liu D, Sun J, et al. Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation. Oncoimmunology. 2016 May. 5 (5):e1139274. [QxMD MEDLINE Link]. [Full Text].
Haque T, Wilkie GM, Jones MM, Higgins CD, Urquhart G, Wingate P. Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007 Aug 15. 110(4):1123-31. [QxMD MEDLINE Link].
Prockop S, Doubrovina E, Suser S, et al. Off-the-shelf EBV-specific T cell immunotherapy for rituximab-refractory EBV-associated lymphoma following transplantation. J Clin Invest. 2020 Feb 3. 130 (2):733-747. [QxMD MEDLINE Link]. [Full Text].
Keam SJ. Tabelecleucel: First Approval. Mol Diagn Ther. 2023 May. 27 (3):425-431. [QxMD MEDLINE Link].
Jain M, Badwal S, Pandey R, Srivastava A, Sharma RK, Gupta RK. Post-transplant lymphoproliferative disorders after live donor renal transplantation. Clin Transplant. 2005 Oct. 19(5):668-73. [QxMD MEDLINE Link].
[Guideline] Styczynski J, van der Velden W, Fox CP, et al. Management of Epstein-Barr Virus infections and post-transplant lymphoproliferative disorders in patients after allogeneic hematopoietic stem cell transplantation: Sixth European Conference on Infections in Leukemia (ECIL-6) guidelines. Haematologica. 2016 Jul. 101 (7):803-11. [QxMD MEDLINE Link]. [Full Text].
Jaksch P, Wiedemann D, Kocher A, Muraközy G, Augustin V, Klepetko W. Effect of Cytomegalovirus Immunoglobulin on the Incidence of Lymphoproliferative Disease After Lung Transplantation: Single-Center Experience With 1157 Patients. Transplantation. 2013 Jan 29. [QxMD MEDLINE Link].
Shahid S, Prockop SE. Epstein-Barr virus-associated post-transplant lymphoproliferative disorders: beyond chemotherapy treatment. Cancer Drug Resist. 2021. 4:646-664. [QxMD MEDLINE Link]. [Full Text].
Twist CJ, Kjelson L, Esquivel CO, Castillo RO. Treatment of recurrent post-transplant lymphoproliferative disorder (PTLD) of the Central Nervous System (CNS) with high-dose methotrexate (HD-MTX). Proceedings of the XIIth International Small Bowel Transplant Symposium. 2011.
Nabors LB, Palmer CA, Julian BA, Przekwas AM, Kew CE. Isolated central nervous system posttransplant lymphoproliferative disorder treated with high-dose intravenous methotrexate. Am J Transplant. 2009 May. 9(5):1243-8. [QxMD MEDLINE Link].
Liu L, Liu Q, Feng S. Management of Epstein-Barr virus-related post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation. Ther Adv Hematol. 2020. 11:2040620720910964. [QxMD MEDLINE Link]. [Full Text].
Czyzewski K, Styczynski J, Krenska A, Debski R, Zajac-Spychala O, Wachowiak J. Intrathecal therapy with rituximab in central nervous system involvement of post-transplant lymphoproliferative disorder. Leuk Lymphoma. 2013 Mar. 54(3):503-6. [QxMD MEDLINE Link].
Izadi M, Fazel M, Saadat SH, Taheri S. Radiotherapy is the best treatment method in post transplant lymphoproliferative disorders localizing in brain: a review of the literature. Ann Transplant. 2011 Oct-Dec. 16(4):126-33. [QxMD MEDLINE Link].
Stocker N, Labopin M, Boussen I, Paccoud O, Bonnin A, Malard F, et al. Pre-emptive rituximab treatment for Epstein-Barr virus reactivation after allogeneic hematopoietic stem cell transplantation is a worthwhile strategy in high-risk recipients: a comparative study for immune recovery and clinical outcomes. Bone Marrow Transplant. 2020 Mar. 55 (3):586-594. [QxMD MEDLINE Link].
Green M. Management of Epstein-Barr virus-induced post-transplant lymphoproliferative disease in recipients of solid organ transplantation. Am J Transplant. 2001 Jul. 1(2):103-8. [QxMD MEDLINE Link].
[Guideline] Allen UD, Preiksaitis JK, AST Infectious Diseases Community of Practice. Post-transplant lymphoproliferative disorders, Epstein-Barr virus infection, and disease in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep. 33 (9):e13652. [QxMD MEDLINE Link].
Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007 Mar 15. 109(6):2571-8. [QxMD MEDLINE Link].
Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine (Baltimore). 1991 Mar. 70(2):137-60. [QxMD MEDLINE Link].
Suryanarayan K, Natkunam Y, Berry G, Bangs CD, Cherry A, Dahl G. Modified cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy for posttransplantation lymphoproliferative disease in pediatric patients undergoing solid organ transplantation. J Pediatr Hematol Oncol. 2001 Oct. 23(7):452-5. [QxMD MEDLINE Link].
Taylor AL, Bowles KM, Callaghan CJ, Wimperis JZ, Grant JW, Marcus RE. Anthracycline-based chemotherapy as first-line treatment in adults with malignant posttransplant lymphoproliferative disorder after solid organ transplantation. Transplantation. 2006 Aug 15. 82(3):375-81. [QxMD MEDLINE Link].
Chan TS, Hwang YY, Gill H, Au WY, Leung AY, Tse E. Post-transplant lymphoproliferative diseases in Asian solid organ transplant recipients: late onset and favorable response to treatment. Clin Transplant. 2012 Sep-Oct. 26(5):679-83. [QxMD MEDLINE Link].
Giraldi E, Provenzi M, Fiocchi R, Colledan M, Cornelli P, Torre G. Fludarabine, cyclophosphamide, doxorubicin (FCD), and rituximab: a remission induction therapy for aggressive pediatric post-transplant lymphoproliferative disease (PTLD). Pediatr Blood Cancer. 2011 Aug. 57(2):324-8. [QxMD MEDLINE Link].
Gupta S, Fricker FJ, González-Peralta RP, Slayton WB, Schuler PM, Dharnidharka VR. Post-transplant lymphoproliferative disorder in children: recent outcomes and response to dual rituximab/low-dose chemotherapy combination. Pediatr Transplant. 2010 Nov. 14(7):896-902. [QxMD MEDLINE Link].
Hatton O, Martinez OM, Esquivel CO. Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder. Pediatr Transplant. 2012 May. 16(3):220-9. [QxMD MEDLINE Link].
Icheva V, Kayser S, Wolff D, Tuve S, Kyzirakos C, Bethge W. Adoptive transfer of epstein-barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013 Jan 1. 31(1):39-48. [QxMD MEDLINE Link].
Kamdar KY, Rooney CM, Heslop HE. Posttransplant lymphoproliferative disease following liver transplantation. Curr Opin Organ Transplant. 2011 Jun. 16(3):274-80. [QxMD MEDLINE Link].
Kasiske BL, Kukla A, Thomas D, Wood Ives J, Snyder JJ, Qiu Y. Lymphoproliferative disorders after adult kidney transplant: epidemiology and comparison of registry report with claims-based diagnoses. Am J Kidney Dis. 2011 Dec. 58(6):971-80. [QxMD MEDLINE Link].
Khedmat H, Taheri S. Lymphoproliferative disorders in pediatric liver allograft recipients: a review of 212 cases. Hematol Oncol Stem Cell Ther. 2012. 5(2):84-90. [QxMD MEDLINE Link].
Manlhiot C, Pollock-Barziv SM, Holmes C, Weitzman S, Allen U, Clarizia NA. Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients. J Heart Lung Transplant. 2010 Jun. 29(6):648-57. [QxMD MEDLINE Link].
Nakanishi C, Kawagishi N, Sekiguchi S, Akamatsu Y, Sato K, Miyagi S. Post-transplantation lymphoproliferative disorder in living-donor liver transplantation: a single-center experience. Surg Today. 2012 Aug. 42(8):741-51. [QxMD MEDLINE Link].
Parker A, Bowles K, Bradley JA, Emery V, Featherstone C, Gupte G, et al. Diagnosis of post-transplant lymphoproliferative disorder in solid organ transplant recipients - BCSH and BTS Guidelines. Br J Haematol. 2010 Apr 16. [QxMD MEDLINE Link].
Reshef R, Vardhanabhuti S, Luskin MR, Heitjan DF, Hadjiliadis D, Goral S. Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder(?). Am J Transplant. 2011 Feb. 11(2):336-47. [QxMD MEDLINE Link].
Scarsbrook AF, Warakaulle DR, Dattani M, Traill Z. Post-transplantation lymphoproliferative disorder: the spectrum of imaging appearances. Clin Radiol. 2005 Jan. 60(1):47-55. [QxMD MEDLINE Link].
Twombley K, Pokala H, Ardura MI, Harker-Murray P, Johnson-Welch SF, Weinberg A. Intraventricular rituximab and systemic chemotherapy for treatment of central nervous system post-transplant lymphoproliferative disorder after kidney transplantation. Pediatr Transplant. 2012 Sep. 16(6):E201-9. [QxMD MEDLINE Link].
Wudhikarn K, Holman CJ, Linan M, Blaes AH, Dunitz JM, Hertz ME. Post-transplant lymphoproliferative disorders in lung transplant recipients: 20-yr experience at the University of Minnesota. Clin Transplant. 2011 Sep-Oct. 25(5):705-13. [QxMD MEDLINE Link].
Yoon SO, Yu E, Cho YM, Suh C, Kim KM, Han DJ. Post-transplant lymphoproliferative disorders: clinicopathological analysis of 43 cases in a single center, 1990-2009. Clin Transplant. 2012 Jan-Feb. 26(1):67-73. [QxMD MEDLINE Link].
Fujimoto A, et al; Complication Working Group of the Japan Society for Hematopoietic Cell Transplantation. Low incidence of posttransplant lymphoproliferative disorder after allogeneic stem cell transplantation in patients with lymphoma treated with rituximab. Hematol Oncol. 2020 Apr. 38 (2):146-152. [QxMD MEDLINE Link].
Van Besien K, Bachier-Rodriguez L, Satlin M, Brown MA, Gergis U, Guarneri D, et al. Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk. Leuk Lymphoma. 2019 Jul. 60 (7):1693-1696. [QxMD MEDLINE Link].

Media Gallery

Biopsy of gingival tissue (400 X) with hematoxylin and eosin stain demonstrates polymorphous infiltrate of atypical lymphoid cells, which is consistent with posttransplant lymphoproliferative disease (PTLD).
Biopsy of gingival tissue (400 X). Epstein-Barr virus encoded RNA (EBER) study shows numerous positive cells, which is consistent with posttransplant lymphoproliferative disease (PTLD).

of 2

Author

Phillip M Garfin, MD, PhD Senior Medical Director, Department of Oncology, Zymeworks Biopharmaceuticals, Inc

Phillip M Garfin, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society for Cell Biology, American Society for Transplantation and Cellular Therapy, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Immunotherapy of Cancer

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Zymeworks inc, Seagen inc.

Coauthor(s)

Clare J Twist, MD Associate Professor of Pediatrics, Division of Hematology/Oncology, Medical Center Line, Stanford University School of Medicine; Medical Staff, Lucile Packard Children’s Hospital and Stanford University Medical Center

Clare J Twist, MD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Marcel E Conrad, MD Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, The Society of Federal Health Professionals (AMSUS), International Society of Hematology, Society for Experimental Biology and Medicine, SWOG

Disclosure: Partner received none from No financial interests for none.

Chief Editor

Ron Shapiro, MD Professor of Surgery, Surgical Director, Kidney/Pancreas Transplant Program, The Recanati/Miller Transplantation Institute at Mount Sinai Hospital

Ron Shapiro, MD is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, American Society of Transplantation, American Surgical Association, Association for Academic Surgery, Central Surgical Association, International Pancreas and Islet Transplant Association, International Pediatric Transplant Association, Society of University Surgeons, Transplantation Society

Disclosure: Nothing to disclose.

Acknowledgements

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Mary Prendergast, MD Department of Internal Medicine, University of Nebraska Medical Center

Mary Prendergast, MD is a member of the following medical societies: Royal College of Physicians

Disclosure: Nothing to disclose.

Vinay Ranga, MD Assistant Professor, Department of Internal Medicine, Division of Nephrology, Hartford Hospital

Disclosure: Nothing to disclose.

Sections Posttransplant Lymphoproliferative Disease (PTLD)
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Questions & Answers
Media Gallery
References

Posttransplant Lymphoproliferative Disease (PTLD) Differential Diagnoses

Diagnostic Considerations

References

Tables

Contributor Information and Disclosures

What would you like to print?