Medscape is available in 5 Language Editions – Choose your Edition here.


Posttransplant Lymphoproliferative Disease Treatment & Management

  • Author: Phillip M Garfin, MD, PhD; Chief Editor: Ron Shapiro, MD  more...
Updated: Apr 09, 2015

Medical Care

The management of posttransplant lymphoproliferative disease (PTLD) remains a challenge and generally without a standardized therapeutic approach that can be applied to all patients. Despite this diversity, reduction of immunosuppression remains the cornerstone for treatment of EBV-driven B-cell PTLD, independent of histology. Starzl et al were the first to suggest reduction, or withdrawal, of immunosuppression as a treatment option for PTLD. This strategy allows the patient's natural immunity to recover and gain control over proliferating EBV-infected cells. Benkerrou et al reported complete regression in 40% of patients after reduction or discontinuation of immunosuppressive therapy. Patients with less-aggressive or polyclonal PTLD tend to respond more favorably to this management approach, as compared to patients with clinically aggressive PTLD.

Additional therapeutic measures that have been used, each with varying degrees of success, include surgical excision of the lesion (which may be curative in cases of localized disease), antiviral therapy, intravenous gamma globulin (IVIG), alfa interferon, radiation therapy and chemotherapy, monoclonal antibodies, and cytotoxic T lymphocytes.[40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52] The choice of therapy ideally attempts to balance the risk of life-threatening PTLD with the risk of allograft failure and treatment-related morbidity. In patients who have undergone solid organ transplantation (SOT), reduction of immunosuppression may risk allograft rejection. In addition, SOT recipients are often at greater risk for organ toxicity and opportunistic infections that may complicate chemotherapy administration. In hematopoietic stem cell transplantation (HSCT) patients with PTLD, reduction of immunosuppression may increase the risk of graft versushost disease.

Antiviral therapy—acyclovir, ganciclovir, or foscarnet—in the absence of reduction of immunosuppression, is not considered effective treatment for PTLD. While these drugs have not shown efficacy as single agent therapy for PTLD, they are often used together with reduction of immunosuppression as a first step in management.[53] B lymphocytes that are latently infected with EBV are generally not susceptible to nucleoside-type antiviral agents, because the viral enzyme target of antiviral drugs, thymidine kinase (TK), is not expressed. However, administration of arginine butyrate has been shown to increase expression of some lytic phase genes, including EBV-TK, in latently infected B cells. In a novel approach to therapy, administration of arginine butyrate together with ganciclovir has been shown to render latently infected and previously antiviral-resistant EBV-lymphoma cells, sensitive to ganciclovir. This strategy remains an investigational but promising new therapy forEBV-PTLD.[54]

Interferon alfa has historically been considered a potential therapeutic option in the treatment of B-cell PTLD.[55, 42, 43] Interferon alfa is recognized to inhibit the outgrowth of EBV-transformed B cells, and it decreases the oropharyngeal shedding of EBV. It also is known to inhibit T helper cells, which release cytokines (ie, interleukin [IL]–4, IL-6, IL-10) that promote B-cell proliferation. Interferon functions as both a proinflammatory and antiviral agent. Because no prospective clinical trials have been conducted to date, many of the reports of its success in the management of PTLD are anecdotal.

IVIG has been used as adjunctive therapy in the management of PTLD. Deficiency or absence of antibody against one of the EBNAs in patients post transplantation has been associated with the subsequent development of PTLD. Decreasing EBV viral load has been reported to be associated with increased levels of antibody against EBNAs. These 2 factors provide the rationale for the use of IVIG in the management of PTLD. IVIG or anticytomegalovirus (CMV) immunoglobulin (CytoGam), which contains anti-EBV antibodies, is most commonly used in conjunction with antiviral therapy as prophylaxis against CMV in SOT or HSCT patients. This anti-CMV prophylactic regimen may also provide some protection against developing EBV-PTLD.[56] In clinical practice, this strategy is frequently initiated in SOT patients with rising EBV viral loads who are considered to be at risk for developing PTLD.

The use of anti–B-cell antibodies as a treatment strategy for a series of patients with PTLD was reported in 1991 by Fischer et al. In that study, 26 patients with B-cell lymphoproliferative syndromes following HSCT and SOT were treated with murine anti-CD21 and anti-CD24 monoclonal antibodies. The authors concluded that anti–B-cell antibodies could be effective treatment for diffuse oligoclonal lymphoproliferative disease, but that monoclonal PTLD or disease involving the CNS did not respond to this therapy.

Benkerrou et al subsequently reported the long-term outcome of 58 patients with PTLD after SOT or bone marrow transplantation who were treated with the same regimen of anti-CD21 and anti-CD24 antibodies. Complete remission was achieved in 61% of patients, with a relapse rate of 8%. The overall long-term survival rate was 46% at 61 months, with survival rates lower among HSCT patients (35%) compared with SOT patients (55%). They also identified multivisceral disease, CNS involvement, and late-onset PTLD as poor prognostic features, consistent with results published by other authors.

More recently, rituximab, a humanized anti-CD20 monoclonal antibody, has been used to treat CD20-expressing non-Hodgkin lymphomas and PTLDs. In 2000, Milpied et al published their retrospective experience of 32 patients with PTLD after SOT or HSCT treated with rituximab and reported an overall response rate of 69%. Subsequently, several reports have also demonstrated the safety and efficacy of single-agent rituximab in the treatment of CD20-expressing PTLD, generally with a response rate of approximately 50%.[57, 58, 59] However, relapse of PTLD is not uncommon after rituximab monotherapy. In addition, the kinetics of disease response to rituximab may be slower than what is observed with chemotherapy, making it a less effective therapeutic option for patients with clinically aggressive or fulminant PTLD. These observations have led investigators to combine rituximab with chemotherapy.

An international multicenter, prospective, phase II trial found rituximab followed by CHOP (cyclophosphamide, Adriamycin, Oncovin, and prednisone) chemotherapy to be a safe and effective treatment for adult SOT patients with PTLD who had previously failed upfront reduction in immunosuppression.[60] Patients received 4 weekly courses of rituximab followed by CHOP. In this study, 60% of the patients had a complete or partial response to rituximab alone, and this overall response rate improved to 90% following CHOP therapy. There was, however, an 11% CHOP-associated mortality rate and a 9% rate of toxicity significant enough to halt CHOP treatment. The authors conclude that sequential first-line therapy with rituximab followed by CHOP chemotherapy is efficacious in the management of PTLD and may be superior to rituximab monotherapy followed by chemotherapy at the time of disease progression or relapse. In this series, patients who were rituximab nonresponders were at greatest risk for treatment-relatedmorbidity and mortality.

Historically, a high mortality rate has been associated with the use of chemotherapy in the management of transplant-associated lymphoproliferative disease.[61] The CHOP combination, which is a standard chemotherapy regimen for non-Hodgkin lymphoma, has been used in patients with PTLD, often achieving high remission rates.[61] A modified CHOP regimen was used in a small series of 6 pediatric patients, with a 67% overall survival rate.[62] However, the toxicities of this regimen were significant, including prolonged myelosuppression and one death from sepsis. In recipients of SOT other than cardiac transplantation, various anthracycline-based regimens have been used with some success.[63] However, SOT patients are often not able to tolerate full-dose chemotherapy owing to end-organ toxicity or risk of allograft dysfunction. For cardiac transplant patients, the dose of doxorubicin is often reduced over concerns of myocardial toxicity. Patients who develop PTLD after HSCT are often notable to tolerate chemotherapy owing to myelotoxicity.

Despite these challenges, with diligent supportive care and careful monitoring for toxicity, chemotherapy can be safely administered to most SOT patients. Given the risk of treatment-related morbidity and mortality, this strategy is often reserved for patients in whom front-line therapy with reduction of immunosuppression and/or rituximab failed, for patients with CD20-negative PTLD, or for patients with clinically fulminant PTLD, including those with CNS involvement.

In an effort to decrease the chemotherapy-related toxicity observed in SOT recipients, a low-dose chemotherapy regimen consisting of cyclophosphamide and prednisone was piloted in 36 children with PTLD in whom initial reduction of immunosuppression failed.[64] The overall response rate was 83%, and 2 patients died of treatment-related toxicity. The PTLD relapse rate was 19%. To further assess the efficacy of this regimen, a Children’s Oncology Group phase II trial of low-dose cyclophosphamide and prednisone together with rituximab was conducted.[65] Fifty-four pediatric patients with PTLD were enrolled in the study, and the majority had monomorphic disease. The complete response rate in this study was 69%, and the 2-year event-free survival rate was 71%; there was one death due to infection during therapy.

For patients with CNS involvement of PTLD, the prognosis remains poor even with aggressive therapy. High-dose methotrexate has been reported to be a tolerable and effective therapy for CNS PTLD.[66, 67, 50] Intrathecal therapy is also considered advisable because many systemic chemotherapy agents and monoclonal antibodies do not cross the blood-brain barrier adequately. Small series have described intrathecal rituximab administered to treat isolated CNS PTLD. One study reported a series of 8 children with isolated CNS PTLD.[68] Seven of the patients responded after a median of 2 courses of rituximab, and the therapy was generally well tolerated. Radiotherapy also remains an effective modality for the treatment of CNS PTLD.[69]

With the understanding that EBV PTLD arises in SOT or HSCT patients in whom the normal balance is disrupted between latently infected B cells and the anti–EBV-specific T-cell response, the idea of using adoptive T-cell immunotherapy presented a logical idea for proof of principle. In 1994, Papadopoulous et al reported on the administration of donor-leukocyte infusions to treat PTLD that had developed in 5 patients following T-cell–depleted allogeneic HSCT. Infusions of unirradiated leukocytes from EBV-seropositive donors resulted in complete clinical responses of PTLD in all patients. However, the infusion of cytotoxic T cells was complicated in some patients by the development of graft versus host disease. Since these early experiments, adoptive immunotherapy techniques have been refined and continue to show promise as a novel therapy for PTLD.

The expanding field of T-cell–based therapy for the treatment of PTLD was reviewed by Heslop in 2012. Donor EBV-specific cytotoxic T lymphocytes administered to HSCT recipients with PTLD have recently been reported to achieve an overall response rate of 68% and without inducing graft versus host disease.[52] The use of donor cytotoxic T lymphocytes is more problematic for SOT patients, and so the development of “third party” EBV cytotoxic T lymphocytes - that could potentially be available from a bank of HLA-typed EBV-specific T-cell lines is being actively investigated.[70, 71] Currently, this approach is available only at a few centers in the United States and has not been adapted for larger-scale production.


In 2012, an international multidisciplinary panel of experts published a consensus statement on the classification and risk factors for PTLD and outlined approaches to minimize the risk of developing PTLD.[3] The first of these recommendations from the Seville Workshop group is that EBV status of both the donor and the recipient should be ascertained prior to donor selection. Whenever possible, EBV-negative recipients should receive grafts from EBV-negative donors.

The next suggestion is to minimize upfront immunosuppression as much as possible and potentially to use reactivation of other viruses, such as CMV or BK virus as cues to reduce immunosuppression. Although antiviral therapy has not proven to be an effective treatment for PTLD, in selected high-risk patients prophylactic or preemptive antiviral therapy may be considered. An alternative approach to antiviral prophylaxis is to administer IVIG or CytoGam to maintain high titers of anti-EBV antibodies that may help prevent the development of EBV PTLD.

The last recommendation from the Seville Workshop is to consider preemptive treatment for those patients who appear to be developing PTLD. A rising EBV viral load in a high-risk patient may warrant preemptive reduction in immunosuppression, while continuing to monitor closely for allograft dysfunction.


Surgical Care

Surgical management alone is rarely the sole mode of therapy for posttransplant lymphoproliferative disease (PTLD). Diagnostic tissue must be obtained for histologic examination in patients with clinical concern for PTLD. Occasionally when PTLD is localized to single nodal or extranodal site (eg, in localized small bowel lesions that present as intussusception), the diagnostic surgical procedure may remove the only site of disease. In such a situation, the decision as to whether the patient will benefit from adjuvant therapy (reduction of immunosuppression, rituximab, or chemotherapy) depends on the pathologic diagnosis and the patient’s individual risk factors.

Contributor Information and Disclosures

Phillip M Garfin, MD, PhD California Institute of Regenerative Medicine MD Training Scholar, Clinical Instructor, Section of Hematology, Oncology, Stem Cell Transplantation, and Cancer Biology, Department of Pediatrics, Stanford University School of Medicine

Phillip M Garfin, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


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, Association of Military Surgeons of the US, 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, Robert J Corry Chair in Transplantation Surgery, Associate Clinical Director, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center

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

Disclosure: Nothing to disclose.


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.

  1. Green M, Webber S. Posttransplantation lymphoproliferative disorders. Pediatr Clin North Am. 2003 Dec. 50(6):1471-91. [Medline].

  2. Swerdlow SH, Webber SA, Chadburn A, Ferry JA. Posttransplant lymphoproliferative disorders. Swerdlow SH, Campo E, Harris NL, Jaffe ES. WHO classification of tumors of haemotopoietic and lymphoid tissue. IARC, Lyon; 2008. 343-350.

  3. 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. [Medline].

  4. Bakker NA, van Imhoff GW. Post-transplant lymphoproliferative disorders: from treatment to early detection and prevention?. Haematologica. 2007 Nov. 92(11):1447-50. [Medline].

  5. 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. [Medline].

  6. Cohen JI. Epstein-Barr virus infection. N Engl J Med. 2000 Aug 17. 343(7):481-92. [Medline].

  7. 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. [Medline].

  8. Epstein MA, Achong BG, Barr YM. Virus particles in cultured lymphoblasts from Burkitt's lymphoma. Lancet. 1964. 1:702-3.

  9. 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. [Medline].

  10. 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. [Medline].

  11. 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. [Medline].

  12. 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. [Medline].

  13. 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. [Medline].

  14. 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. [Medline].

  15. 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. [Medline].

  16. 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. [Medline].

  17. 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. [Medline].

  18. 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. [Medline].

  19. LaCasce AS. Post-transplant lymphoproliferative disorders. Oncologist. 2006 Jun. 11(6):674-80. [Medline].

  20. Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2004 Aug 11.

  21. 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. [Medline].

  22. 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. [Medline].

  23. 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. [Medline].

  24. 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. [Medline].

  25. 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. [Medline].

  26. 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. [Medline].

  27. 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. [Medline].

  28. 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. [Medline].

  29. 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. [Medline].

  30. 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. [Medline].

  31. 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. [Medline].

  32. 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. [Medline].

  33. 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. [Medline].

  34. 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. [Medline].

  35. 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. [Medline].

  36. 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. [Medline].

  37. 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. [Medline].

  38. 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. [Medline].

  39. 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. [Medline].

  40. 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. [Medline].

  41. 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. [Medline].

  42. 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. [Medline].

  43. 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. [Medline].

  44. 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. [Medline].

  45. 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. [Medline].

  46. 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. [Medline].

  47. 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. [Medline].

  48. Becker YT, Samaniego-Picota M, Sollinger HW. The emerging role of rituximab in organ transplantation. Transpl Int. 2006 Aug. 19(8):621-8. [Medline].

  49. 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. [Medline].

  50. 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. [Medline].

  51. 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. [Medline].

  52. 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. [Medline].

  53. 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. [Medline].

  54. 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. [Medline].

  55. Hartmann C, Schuchmann M, Zimmermann T. Posttransplant lymphoproliferative disease in liver transplant patients. Curr Infect Dis Rep. 2011 Feb. 13(1):53-9. [Medline].

  56. 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. [Medline].

  57. 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. [Medline].

  58. 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. [Medline].

  59. 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. [Medline].

  60. 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. [Medline].

  61. Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine (Baltimore). 1991 Mar. 70(2):137-60. [Medline].

  62. 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. [Medline].

  63. 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. [Medline].

  64. 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. [Medline].

  65. 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. [Medline].

  66. 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.

  67. 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. [Medline].

  68. 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. [Medline].

  69. 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. [Medline].

  70. 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. [Medline].

  71. Sun Q, Burton R, Reddy V, Lucas KG. Safety of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes for patients with refractory EBV-related lymphoma. Br J Haematol. 2002 Sep. 118(3):799-808. [Medline].

  72. 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. [Medline].

  73. Borenstein J, Pezzella F, Gatter KC. Plasmablastic lymphomas may occur as post-transplant lymphoproliferative disorders. Histopathology. 2007 Dec. 51(6):774-7. [Medline].

  74. Brunner B, Kropshofer G, Ellemunter H, Brunner A, Mueller T, Margreiter R. Severe cold agglutinin disease caused by recurrent monomorphic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD), clonally related to an EBV-negative plasmacytic hyperplasia in a pediatric multivisceral organ transplant recipient. Pediatr Transplant. 2007 Aug. 11(5):547-51. [Medline].

  75. Buadi FK, Heyman MR, Gocke CD, et al. Treatment and outcomes of post-transplant lymphoproliferative disease: a single institution study. Am J Hematol. 2007 Mar. 82(3):208-14. [Medline].

  76. 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. [Medline].

  77. Comoli P, Maccario R, Locatelli F, et al. Treatment of EBV-related post-renal transplant lymphoproliferative disease with a tailored regimen including EBV-specific T cells. Am J Transplant. 2005 Jun. 5(6):1415-22. [Medline].

  78. Dharnidharka VR, Araya CE. Post-transplant lymphoproliferative disease. Pediatr Nephrol. 2009 Apr. 24(4):731-6. [Medline].

  79. Dharnidharka VR, Talley LI, Martz KL, Stablein DM, Fine RN. Recombinant growth hormone use pretransplant and risk for post-transplant lymphoproliferative disease--a report of the NAPRTCS. Pediatr Transplant. 2008 Sep. 12(6):689-95. [Medline].

  80. Dhillon MS, Rai JK, Gunson BK, Olliff S, Olliff J. Post-transplant lymphoproliferative disease in liver transplantation. Br J Radiol. 2007 May. 80(953):337-46. [Medline].

  81. Doesch AO, Konstandin M, Celik S, Kristen A, Frankenstein L, Sack FU. Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients. Transpl Int. 2008 Oct. 21(10):963-71. [Medline].

  82. Evens MA, David KA, Helenowski I, et al. Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease. J Clin Oncol. 2010. 28:1038-1046.

  83. Fohrer C, Cailliard S, Koumarianou A. Long term survival in post-transplatn lymphoproliferative disorders with a dose-adjusted ACVBP regimen. Br J Hematol. 2006. 134:601-12. [Medline].

  84. Gautam A, Morrissey PE, Brem AS, et al. Use of an immune function assay to monitor immunosuppression for treatment of post-transplant lymphoproliferative disorder. Pediatr Transplant. 2006 Aug. 10(5):613-6. [Medline].

  85. Ghobrial IM, Habermann TM, Ristow KM, Ansell SM, Macon W, Geyer SM. Prognostic factors in patients with post-transplant lymphoproliferative disorders (PTLD) in the rituximab era. Leuk Lymphoma. 2005 Feb. 46(2):191-6. [Medline].

  86. 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. [Medline].

  87. Gross TG. Post-transplant lymphoproliferative disease in children following solid organ transplant and rituximab--the final answer?. Pediatr Transplant. 2007 Sep. 11(6):575-7. [Medline].

  88. 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. [Medline].

  89. 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. [Medline].

  90. Hayashida M, Ogita K, Matsuura T, Takahashi Y, Nishimoto Y, Ohga S. Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child. Pediatr Transplant. 2007 Sep. 11(6):671-5. [Medline].

  91. Heslop HE. Equal-opportunity treatment of EBV-PTLD. Blood. 2012 Mar 15. 119(11):2436-8. [Medline].

  92. Hourigan MJ, Doecke J, Mollee PN, Gill DS, Norris D, Johnson DW. A new prognosticator for post-transplant lymphoproliferative disorders after renal transplantation. Br J Haematol. 2008 Jun. 141(6):904-7. [Medline].

  93. 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. [Medline].

  94. Kamdar KY, Rooney CM, Heslop HE. Posttransplant lymphoproliferative disease following liver transplantation. Curr Opin Organ Transplant. 2011 Jun. 16(3):274-80. [Medline].

  95. 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. [Medline].

  96. Kessler M, Jay N, Molle R, Guillemin F. Excess risk of cancer in renal transplant patients. Transpl Int. 2006 Nov. 19(11):908-14. [Medline].

  97. Kharfan-Dabaja MA, Bazarbachi A. Emerging role of CD20 blockade in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010 Oct. 16(10):1347-54. [Medline].

  98. 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. [Medline].

  99. 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. [Medline].

  100. 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. [Medline].

  101. 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. [Medline].

  102. 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. [Medline].

  103. Rinaldi A, Kwee I, Poretti G, Mensah A, Pruneri G, Capello D. Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas. Br J Haematol. 2006 Jul. 134(1):27-36. [Medline].

  104. 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. [Medline].

  105. 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. [Medline].

  106. 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. [Medline].

  107. Wasson S, Zafar MN, Best J, Reddy HK. Post-transplantation lymphoproliferative disorder in heart and kidney transplant patients: a single-center experience. J Cardiovasc Pharmacol Ther. 2006 Mar. 11(1):77-83. [Medline].

  108. 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. [Medline].

  109. 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. [Medline].

  110. 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. [Medline].

  111. 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. [Medline].

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).
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.