Top

Published in:

01-09-2013 | Lymphomas (C Dearden, Section Editor)

Post-Transplant Lymphoproliferative Disease (PTLD): Risk Factors, Diagnosis, and Current Treatment Strategies

Authors: Zeina Al-Mansour, Beverly P. Nelson, Andrew M. Evens

Published in: Current Hematologic Malignancy Reports | Issue 3/2013

Abstract

Post-transplant lymphoproliferative diseases (PTLD) are heterogeneous lymphoid disorders ranging from indolent polyclonal proliferations to aggressive lymphomas that complicate solid organ or hematopoietic transplantation. Risk factors for PTLD include viral infections, degree of immunosuppression, recipient age and race, allograft type, and host genetic variations. Clinically, extra-nodal disease is common including 10–15 % presenting with central nervous system (CNS) disease. Most PTLD cases are B cell (5-10 % T/NK cell or Hodgkin lymphoma), while over one-third are EBV-negative. World Health Organization (WHO) diagnostic categories are: early lesions, polymorphic, and monomorphic PTLD; although in practice, a clear separation is not always possible. Therapeutically, reduction in immunosuppression remains a mainstay, and recent data has documented the importance of rituximab +/- combination chemotherapy. Therapy for primary CNS PTLD should be managed according to immunocompetent CNS paradigms. Finally, novel treatment strategies for PTLD have emerged, including adoptive immunotherapy and rational targeted therapeutics (e.g., anti-CD30 based therapy and downstream signaling pathways of latent membrane protein-2A).

Doak PB, Montgomerie JZ, North JD, Smith F. Reticulum cell sarcoma after renal homotransplantation and azathioprine and prednisone therapy. Br Med J. 1968;4(5633):746–8.PubMedCrossRef

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;1(8377):583–7.PubMedCrossRef

Bhatia S, Ramsay NK, Steinbuch M, Dusenbery KE, Shapiro RS, Weisdorf DJ, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87(9):3633–9.PubMed

Shapiro RS, McClain K, Frizzera G, Gajl-Peczalska KJ, Kersey JH, Blazar BR, et al. Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood. 1988;71(5):1234–43.PubMed

Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet. 1993;342(8886–8887):1514–6.PubMedCrossRef

Cockfield SM. Identifying the patient at risk for post-transplant lymphoproliferative disorder. Transpl Infect Dis. 2001;3(2):70–8.PubMedCrossRef

Opelz G, Dohler B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(2):222–30.PubMedCrossRef

Caillard S, Lelong C, Pessione F, Moulin B, French PWG. Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry. Am J Transplant. 2006;6(11):2735–42.PubMedCrossRef

Hartmann C, Schuchmann M, Zimmermann T. Posttransplant lymphoproliferative disease in liver transplant patients. Curr Infect Dis Rep. 2011;13(1):53–9.PubMedCrossRef

10.

Leblond V, Dhedin N, Mamzer Bruneel MF, Choquet S, Hermine O, Porcher R, et al. Identification of prognostic factors in 61 patients with posttransplantation lymphoproliferative disorders. J Clin Oncol. 2001;19(3):772–8.PubMed

11.

Ghobrial IM, Habermann TM, Maurer MJ, Geyer SM, Ristow KM, Larson TS, et al. Prognostic analysis for survival in adult solid organ transplant recipients with post-transplantation lymphoproliferative disorders. J Clin Oncol. 2005;23(30):7574–82.PubMedCrossRef

12.

Dotti G, Fiocchi R, Motta T, Mammana C, Gotti E, Riva S, et al. Lymphomas occurring late after solid-organ transplantation: influence of treatment on the clinical outcome. Transplantation. 2002;74(8):1095–102.PubMedCrossRef

13.

• Evens AM, David KA, Helenowski I, Nelson B, Kaufman D, Kircher SM, 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(6):1038–46. This was a multicenter retrospective analysis of 80 PTLD patients treated over a recent 10-year period. There appeared to be improved survival among patients treated with rituximab-based therapy. PubMedCrossRef

14.

•• Trappe R, Oertel S, Leblond V, Mollee P, Sender M, Reinke P, 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(2):196–206. This was the largest prospective PTLD clinical study conducted to date; it showed the feasibility of sequential rituximab therapy followed by CHOP. Outcomes appeared improved compared with historical controls. The study was modified to a 'risk stratified' approach; the results from this treatment strategy are eagerly awaited. PubMedCrossRef

15.

Ghobrial IM, Habermann TM, Ristow KM, Ansell SM, Macon W, Geyer SM, et al. Prognostic factors in patients with post-transplant lymphoproliferative disorders (PTLD) in the rituximab era. Leuk Lymphoma. 2005;46(2):191–6.PubMedCrossRef

16.

Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI. Aggressive treatment for postcardiac transplant lymphoproliferation. Blood. 1995;86(9):3333–40.PubMed

17.

• 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 center. J Clin Oncol. 2009;27(20):3354–62. The authors examined 7,040 patients who received SOT from 1964 to 2007, from which 78 patients developed PTLD. They assessed risk factors for development of PTLD and compared outcomes with a SEER population sample. PubMedCrossRef

18.

Jagadeesh D, Woda BA, Draper J, Evens AM. Post transplant lymphoproliferative disorders: risk, classification, and therapeutic recommendations. Curr Treat Options in Oncol. 2012;13(1):122–36.CrossRef

19.

Zimmermann H, Reinke P, Neuhaus R, Lehmkuhl H, Oertel S, Atta J, et al. Burkitt post-transplantation lymphoma in adult solid organ transplant recipients: sequential immunochemotherapy with rituximab (R) followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or R-CHOP is safe and effective in an analysis of 8 patients. Cancer. 2012;118(19):4715–24.PubMedCrossRef

20.

Loren AW, Porter DL, Stadtmauer EA, Tsai DE. Post-transplant lymphoproliferative disorder: a review. Bone Marrow Transplant. 2003;31(3):145–55.PubMedCrossRef

21.

Oton AB, Wang H, Leleu X, Melhem MF, George D, Lacasce A, et al. Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders in solid transplant. Leuk Lymphoma. 2008;49(9):1738–44.PubMedCrossRef

22.

Johnson LR, Nalesnik MA, Swerdlow SH. Impact of Epstein-Barr virus in monomorphic B cell posttransplant lymphoproliferative disorders: a histogenetic study. Am J Surg Pathol. 2006;30(12):1604–12.PubMedCrossRef

23.

Novoa-Takara L, Perkins SL, Qi D, Shidham VB, Vesole DH, Hariharan S, et al. Histogenetic phenotypes of B cells in posttransplant lymphoproliferative disorders by immunohistochemical analysis correlate with transplant type: solid organ vs hematopoietic stem cell transplantation. Am J Clin Pathol. 2005;123(1):104–12.PubMedCrossRef

24.

Paya CV, Fung JJ, Nalesnik MA, Kieff E, Green M, Gores G, et al. Epstein-Barr virus-induced posttransplant lymphoproliferative disorders. ASTS/ASTP EBV-PTLD Task Force and The Mayo Clinic Organized International Consensus Development Meeting. Transplantation. 1999;68(10):1517–25.PubMedCrossRef

25.

Nourse JP, Jones K, Gandhi MK. Epstein-Barr Virus-related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy. Am J Transplant. 2011;11(5):888–95.PubMedCrossRef

26.

McDonald RA, Smith JM, Ho M, Lindblad R, Ikle D, Grimm P, et al. Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids. Am J Transplant. 2008;8(5):984–9.PubMedCrossRef

27.

Schaffer K, Hassan J, Staines A, Coughlan S, Holder P, Tuite G, et al. Surveillance of Epstein-Barr virus loads in adult liver transplantation: associations with age, sex, posttransplant times, and transplant indications. Liver Transplant. 2011;17(12):1420–6.CrossRef

28.

Humar A, Michaels M. Monitoring AIWGoID. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006;6(2):262–74.PubMedCrossRef

29.

Stevens SJ, Verschuuren EA, Pronk I, van Der Bij W, Harmsen MC, The TH, et al. Frequent monitoring of Epstein-Barr virus DNA load in unfractionated whole blood is essential for early detection of posttransplant lymphoproliferative disease in high-risk patients. Blood. 2001;97(5):1165–71.PubMedCrossRef

30.

Buda A, Caforio A, Calabrese F, Fagiuoli S, Pevere S, Livi U, et al. Lymphoproliferative disorders in heart transplant recipients: role of hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection. Transplant Int. 2000;13 Suppl 1:S402–5.

31.

Manez R, Breinig MC, Linden P, Wilson J, Torre-Cisneros J, Kusne S, et al. Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus disease. J Infect Dis. 1997;176(6):1462–7.PubMedCrossRef

32.

Tsao L, Hsi ED. The clinicopathologic spectrum of posttransplantation lymphoproliferative disorders. Arch Pathol Lab Med. 2007;131(8):1209–18.PubMed

33.

Dharnidharka VR, Sullivan EK, Stablein DM, Tejani AH, Harmon WE. North American Pediatric Renal Transplant Cooperative S. Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation. 2001;71(8):1065–8.PubMedCrossRef

34.

Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 2005;80(9):1233–43.PubMedCrossRef

35.

Gerritsen EJ, Stam ED, Hermans J, van den Berg H, Haraldsson A, van Tol MJ, et al. Risk factors for developing EBV-related B cell lymphoproliferative disorders (BLPD) after non-HLA-identical BMT in children. Bone Marrow Transplant. 1996;18(2):377–82.PubMed

36.

Zutter MM, Martin PJ, Sale GE, Shulman HM, Fisher L, Thomas ED, et al. Epstein-Barr virus lymphoproliferation after bone marrow transplant. Blood. 1988;72(2):520–9.PubMed

37.

Shapiro R, Nalesnik M, McCauley J, Fedorek S, Jordan ML, Scantlebury VP, et al. Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression. Transplantation. 1999;68(12):1851–4.PubMedCrossRef

38.

Nee R, Hurst FP, Dharnidharka VR, Jindal RM, Agodoa LY, Abbott KC. Racial variation in the development of posttransplant lymphoproliferative disorders after renal transplantation. Transplantation. 2011;92(2):190–5.PubMedCrossRef

39.

VanBuskirk AM, Malik V, Xia D, Pelletier RP. A gene polymorphism associated with posttransplant lymphoproliferative disorder. Transplant Proc. 2001;33(1–2):1834.PubMedCrossRef

40.

Lee TC, Savoldo B, Barshes NR, Rooney CM, Heslop HE, Gee AP, et al. Use of cytokine polymorphisms and Epstein-Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients. Clin Transplant. 2006;20(3):389–93.PubMedCrossRef

41.

Babel N, Vergopoulos A, Trappe RU, Oertel S, Hammer MH, Karaivanov S, et al. Evidence for genetic susceptibility towards development of posttransplant lymphoproliferative disorder in solid organ recipients. Transplantation. 2007;84(3):387–91.PubMedCrossRef

42.

Reshef R, Luskin MR, Kamoun M, Vardhanabhuti S, Tomaszewski JE, Stadtmauer EA, et al. Association of HLA polymorphisms with post-transplant lymphoproliferative disorder in solid-organ transplant recipients. Am J Transplant. 2011;11(4):817–25.PubMedCrossRef

43.

Subklewe M, Marquis R, Choquet S, Leblond V, Garnier JL, Hetzer R, et al. Association of human leukocyte antigen haplotypes with posttransplant lymphoproliferative disease after solid organ transplantation. Transplantation. 2006;82(8):1093–100.PubMedCrossRef

44.

Pourfarziani V, Einollahi B, Taheri S, Nemati E, Nafar M, Kalantar E. Associations of Human Leukocyte Antigen (HLA) haplotypes with risk of developing lymphoproliferative disorders after renal transplantation. Ann Transplant. 2007;12(4):16–22.PubMed

45.

Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ, van der Heide JJ, Lems SP, et al. HLA antigens and post renal transplant lymphoproliferative disease: HLA-B matching is critical. Transplantation. 2005;80(5):595–9.PubMedCrossRef

46.

McAulay KA, Haque T, Crawford DH. Tumour necrosis factor gene polymorphism: a predictive factor for the development of post-transplant lymphoproliferative disease. Br J Canc. 2009;101(6):1019–27.CrossRef

47.

Swerdlow SH. T cell and NK cell posttransplantation lymphoproliferative disorders. Am J Clin Pathol. 2007;127(6):887–95.PubMedCrossRef

48.

Swerdlow SH, International Agency for Research on Cancer, World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: International Agency for Research on Cancer; 2008.

49.

Nalesnik MA. The diverse pathology of post-transplant lymphoproliferative disorders: the importance of a standardized approach. Transpl Infect Dis. 2001;3(2):88–96.PubMedCrossRef

50.

Knowles DM, Cesarman E, Chadburn A, Frizzera G, Chen J, Rose EA, et al. Correlative morphologic and molecular genetic analysis demonstrates three distinct categories of posttransplantation lymphoproliferative disorders. Blood. 1995;85(2):552–65.PubMed

51.

Nelson BP, Wolniak KL, Evens A, Chenn A, Maddalozzo J, Proytcheva M. Early posttransplant lymphoproliferative disease: clinicopathologic features and correlation with mTOR signaling pathway activation. Am J Clin Pathol. 2012;138(4):568–78.PubMedCrossRef

52.

Chadburn A, Cesarman E, Knowles DM. Molecular pathology of posttransplantation lymphoproliferative disorders. Semin Diagn Pathol. 1997;14(1):15–26.PubMed

53.

•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;149(5):675–92. Excellent review of the literature on diagnosis and management of PTLD from a British joint working group.PubMedCrossRef

54.

Djokic M, Le Beau MM, Swinnen LJ, Smith SM, Rubin CM, Anastasi J, et al. Post-transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities. Gene Chromosome Canc. 2006;45(3):313–8.CrossRef

55.

Vegso G, Hajdu M, Sebestyen A. Lymphoproliferative disorders after solid organ transplantation-classification, incidence, risk factors, early detection and treatment options. Pathol Oncol Res. 2011;17(3):443–54.PubMedCrossRef

56.

Leblond V, Davi F, Charlotte F, Dorent R, Bitker MO, Sutton L, et al. Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity? J Clin Oncol. 1998;16(6):2052–9.PubMed

57.

Nelson BP, Nalesnik MA, Bahler DW, Locker J, Fung JJ, Swerdlow SH. Epstein-Barr virus-negative post-transplant lymphoproliferative disorders: a distinct entity? Am J Surg Pathol. 2000;24(3):375–85.PubMedCrossRef

58.

Elstrom RL, Andreadis C, Aqui NA, Ahya VN, Bloom RD, Brozena SC, et al. Treatment of PTLD with rituximab or chemotherapy. Am J Transplant. 2006;6(3):569–76.PubMedCrossRef

59.

Maecker B, Jack T, Zimmermann M, Abdul-Khaliq H, Burdelski M, Fuchs A, et al. CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organ transplantation. J Clin Oncol. 2007;25(31):4902–8.PubMedCrossRef

60.

Knight J, Tsodikov A, Cibrik D, Ross C, Kaminski M, Blayney D. Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center. J Clin Oncol. 2009;27:1–12.CrossRef

61.

Buell JF, Gross TG, Hanaway MJ, Trofe J, Roy-Chaudhury P, First MR, et al. Posttransplant lymphoproliferative disorder: significance of central nervous system involvement. Transplant Proc. 2005;37(2):954–5.PubMedCrossRef

62.

Penn I, Porat G. Central nervous system lymphomas in organ allograft recipients. Transplantation. 1995;59(2):240–4.PubMed

63.

Cavaliere R, Petroni G, Lopes MB, Schiff D, International Primary Central Nervous System Lymphoma Collaborative G. Primary central nervous system post-transplantation lymphoproliferative disorder: an International Primary Central Nervous System Lymphoma Collaborative Group Report. Cancer. 2010;116(4):863–70.PubMedCrossRef

64.

Boubenider S, Hiesse C, Goupy C, Kriaa F, Marchand S, Charpentier B. Incidence and consequences of post-transplantation lymphoproliferative disorders. J Nephrol. 1997;10(3):136–45.PubMed

65.

Dror Y, Greenberg M, Taylor G, Superina R, Hebert D, West L, et al. Lymphoproliferative disorders after organ transplantation in children. Transplantation. 1999;67(7):990–8.PubMedCrossRef

66.

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(12):2954–60.PubMedCrossRef

67.

Penn I, Hammond W, Brettschneider L, Starzl TE. Malignant lymphomas in transplantation patients. Transplant Proc. 1969;1(1):106–12.PubMed

68.

• Reshef R, Vardhanabhuti S, Luskin MR, Heitjan DF, Hadjiliadis D, Goral S, et al. Reduction of immunosuppression as initial therapy for posttransplantation lymphoproliferative disorder( bigstar). Am J Transplant. 2011;11(2):336–47. This was an important analysis of a large cohort of PTLD patients treated with reduced immunosuppression alone. They authors identified risk factors predictive of response to this treatment strategy. PubMedCrossRef

69.

Trofe J, Buell JF, Beebe TM, Hanaway MJ, First MR, Alloway RR, et al. Analysis of factors that influence survival with post-transplant lymphoproliferative disorder in renal transplant recipients: the Israel Penn International Transplant Tumor Registry experience. Am J Transplant. 2005;5(4 Pt 1):775–80.PubMedCrossRef

70.

Faull RJ, Hollett P, McDonald SP. Lymphoproliferative disease after renal transplantation in Australia and New Zealand. Transplantation. 2005;80(2):193–7.PubMedCrossRef

71.

Choquet S, Leblond V, Herbrecht R, Socie G, Stoppa AM, Vandenberghe P, 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(8):3053–7.PubMedCrossRef

72.

Milpied N, Vasseur B, Parquet N, Garnier JL, Antoine C, Quartier P, 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.PubMedCrossRef

73.

Jain AB, Marcos A, Pokharna R, Shapiro R, Fontes PA, Marsh W, et al. Rituximab (chimeric anti-CD20 antibody) for posttransplant lymphoproliferative disorder after solid organ transplantation in adults: long-term experience from a single center. Transplantation. 2005;80(12):1692–8.PubMedCrossRef

74.

Gonzalez-Barca E, Domingo-Domenech E, Capote FJ, Gomez-Codina J, Salar A, Bailen A, et al. Prospective phase II trial of extended treatment with rituximab in patients with B cell post-transplant lymphoproliferative disease. Haematologica. 2007;92(11):1489–94.PubMedCrossRef

75.

Mamzer-Bruneel MF, Lome C, Morelon E, Levy V, Bourquelot P, Jacobs F, et al. Durable remission after aggressive chemotherapy for very late post-kidney transplant lymphoproliferation: A report of 16 cases observed in a single center. J Clin Oncol. 2000;18(21):3622–32.PubMed

76.

Fohrer C, Caillard S, Koumarianou A, Ellero B, Woehl-Jaegle ML, Meyer C, et al. Long-term survival in post-transplant lymphoproliferative disorders with a dose-adjusted ACVBP regimen. Br J Haematol. 2006;134(6):602–12.PubMedCrossRef

77.

Giraldi E, Provenzi M, Fiocchi R, Colledan M, Cornelli P, Torre G, et al. Fludarabine, cyclophosphamide, doxorubicin (FCD), and rituximab: a remission induction therapy for aggressive pediatric post-transplant lymphoproliferative disease (PTLD). Pediatr Blood Canc. 2011;57(2):324–8.CrossRef

78.

Choquet S, Trappe R, Leblond V, Jager U, Davi F, Oertel S. CHOP-21 for the treatment of post-transplant lymphoproliferative disorders (PTLD) following solid organ transplantation. Haematologica. 2007;92(2):273–4.PubMedCrossRef

79.

Tsai DE, Hardy CL, Tomaszewski JE, Kotloff RM, Oltoff KM, Somer BG, et al. Reduction in immunosuppression as initial therapy for posttransplant lymphoproliferative disorder: analysis of prognostic variables and long-term follow-up of 42 adult patients. Transplantation. 2001;71(8):1076–88.PubMedCrossRef

80.

Nalesnik MA, Rao AS, Furukawa H, Pham S, Zeevi A, Fung JJ, et al. Autologous lymphokine-activated killer cell therapy of Epstein-Barr virus-positive and -negative lymphoproliferative disorders arising in organ transplant recipients. Transplantation. 1997;63(9):1200–5.PubMedCrossRef

81.

Rooney CM, Smith CA, Ng CY, Loftin S, Li C, Krance RA, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345(8941):9–13.PubMedCrossRef

82.

Papadopoulos EB, Ladanyi M, Emanuel D, Mackinnon S, Boulad F, Carabasi MH, et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. New Engl J Med. 1994;330(17):1185–91.PubMedCrossRef

83.

Haque T, Wilkie GM, Jones MM, Higgins CD, Urquhart G, Wingate P, et al. Allogeneic cytotoxic T cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007;110(4):1123–31.PubMedCrossRef

84.

Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998;92(5):1549–55.PubMed

85.

Gustafsson A, Levitsky V, Zou JZ, Frisan T, Dalianis T, Ljungman P, et al. Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood. 2000;95(3):807–14.PubMed

86.

Perrine SP, Hermine O, Small T, Suarez F, O'Reilly R, Boulad F, et al. A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007;109(6):2571–8.PubMedCrossRef

87.

Haddad E, Paczesny S, Leblond V, Seigneurin JM, Stern M, Achkar A, 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(6):1590–7.PubMedCrossRef

88.

Davis CL, Wood BL, Sabath DE, Joseph JS, Stehman-Breen C, Broudy VC. Interferon-alpha treatment of posttransplant lymphoproliferative disorder in recipients of solid organ transplants. Transplantation. 1998;66(12):1770–9.PubMedCrossRef

89.

Komrokji RS, Oliva JL, Zand M, Felgar R, Abboud CN. Mini-BEAM and autologous hematopoietic stem cell transplant for treatment of post-transplant lymphoproliferative disorders. Am J Hematol. 2005;79(3):211–5.PubMedCrossRef

90.

Williams KM, Higman MA, Chen AR, Schwartz CL, Wharam M, Colombani P, et al. Successful treatment of a child with late-onset T cell post-transplant lymphoproliferative disorder/lymphoma. Pediatr Blood Canc. 2008;50(3):667–70.CrossRef

91.

Bobey NA, Stewart DA, Woodman RC. Successful treatment of posttransplant lymphoproliferative disorder in a renal transplant patient by autologous peripheral blood stem cell transplantation. Leuk Lymphoma. 2002;43(12):2421–3.PubMedCrossRef

92.

Mahe B, Moreau P, Le Tortorec S, Hourmant M, Harousseau JL, Milpied N. Autologous bone marrow transplantation for cyclosporin-related lymphoma in a renal transplant patient. Bone Marrow Transplant. 1994;14(4):645–6.PubMed

93.

Haque T, Chaggar T, Schafers J, Atkinson C, McAulay KA, Crawford DH. Soluble CD30: a serum marker for Epstein-Barr virus-associated lymphoproliferative diseases. J Med Virol. 2011;83(2):311–6.PubMedCrossRef

94.

Majewski M, Korecka M, Kossev P, Li S, Goldman J, Moore J, et al. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: a potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. PNAS. 2000;97(8):4285–90.PubMedCrossRef

95.

Kirk AD, Cherikh WS, Ring M, Burke G, Kaufman D, Knechtle SJ, et al. Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. Am J Transplant. 2007;7(11):2619–25.PubMedCrossRef

96.

Rovedo M, Longnecker R. Epstein-Barr virus latent membrane protein 2A preferentially signals through the Src family kinase Lyn. J Virol. 2008;82(17):8520–8.PubMedCrossRef

97.

•• Bieging KT, Fish K, Bondada S, Longnecker R. A shared gene expression signature in mouse models of EBV-associated and non-EBV-associated Burkitt lymphoma. Blood. 2011;118(26):6849–59. Important analysis examining the pathogenesis of EBV-related lymphomas. The integral involvement of LMP2A in this process was elucidated.PubMedCrossRef

98.

Fukuda M, Longnecker R. Epstein-Barr virus latent membrane protein 2A mediates transformation through constitutive activation of the Ras/PI3-K/Akt Pathway. J Virol. 2007;81(17):9299–306.PubMedCrossRef

99.

• Evens AM Choquet S, Kroll-Desrosiers AR, et al. Primary CNS Post-Transplant Lymphoproliferative Disease (PTLD): An International Report of 84 Cases in the Modern Era. Am J Transplant, 2013. This is the largest report of primary CNS PTLD; it was an international collaboration of 84 such patients. Outcomes were overall modest, although long-term survival was achieved in 35–40 % of patients. Treatment paradigms similar to immunocompetent CNS lymphomas appeared important.

100.

Taj MM, Messahel B, Mycroft J, Pritchard-Jones K, Baker A, Height S, et al. 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;140(2):191–6.PubMedCrossRef

Title: Post-Transplant Lymphoproliferative Disease (PTLD): Risk Factors, Diagnosis, and Current Treatment Strategies
Authors: Zeina Al-Mansour
Beverly P. Nelson
Andrew M. Evens
Publication date: 01-09-2013
Publisher: Springer US
Published in: Current Hematologic Malignancy Reports / Issue 3/2013
Print ISSN: 1558-8211
Electronic ISSN: 1558-822X
DOI: https://doi.org/10.1007/s11899-013-0162-5

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

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

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

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

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

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2013

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Systematic Review of the Literature and Mini-Meta Analysis

Hairy Cell Leukemia—New Genes, New Targets

Hodgkin Lymphoma in Pregnancy

The Role of Radiation Therapy in the Treatment of Stage I-II Diffuse Large B-Cell Lymphoma

Surveillance Imaging in Pediatric Hodgkin Lymphoma

T-Cell Receptor Signaling in Peripheral T-Cell Lymphoma – A Review of Patterns of Alterations in a Central Growth Regulatory Pathway

Keynote webinar | Spotlight on medication adherence

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

At a glance: The STEP trials