Skip to main content

Advertisement

SpringerLink
Log in

Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation

  • Review Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a well recognized and potentially fatal complication after pediatric cardiac transplantation. PTLD encompasses a wide spectrum, ranging from benign hyperplasia to more aggressive lymphoma. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors resulting from impaired immunity due to immunosuppressive therapy. Pediatric recipients, often seronegative for EBV at transplantation, have a greater risk for PTLD than adults. The clinical presentation of PTLD varies from isolated lymphadenopathy to systemic disease; common sites involved are gastrointestinal tract, lung or airway, and cervical lesions. Timely and accurate diagnosis based on histological examination of biopsy tissue is essential for early intervention. Immunostaining for EBV and evaluation for clonality are needed. For prophylaxis when EBV viral loads are increasing or for initial treatment of early lesions or polymorphic PTLD, a reduction in immunosuppressive treatment is a key component of therapy, but caution is needed for possible rebound allograft rejection. Chemotherapy is indicated for patients with poor response to reduced immunosuppression and for highly aggressive monomorphic PTLD. The use of rituximab in combination with chemotherapy is effective. For the time being, avoiding excessive immunosuppression is the most effective strategy for reducing the incidence of PTLD. Calcineurin inhibitor (CNI) minimization with proliferation signal inhibitors (PSIs) or conversion from a CNI to a PSI might be useful for preventing both development of PTLD and allograft rejection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Boucek MM, Waltz DA, Edwards LB, Taylor DO, Keck BM, Trulock EP, et al. Registry of the International Society for Heart and Lung Transplantation: ninth official pediatric heart transplantation report—2006. J Heart Lung Transplant. 2006;25:893–903.

    Article  PubMed  Google Scholar 

  2. Preiksaitis JK. New developments in the diagnosis and management of posttransplantation lymphoproliferative disorders in solid organ transplant recipients. Clin Infect Dis. 2004;39:1016–23.

    Article  PubMed  Google Scholar 

  3. Shaknovich R, Basso K, Bhagat G, Mansukhani M, Hatzivassiliou G, Murty VV, 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;91:1313–20.

    CAS  PubMed  Google Scholar 

  4. Klein E, Kis LL, Klein G. Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions. Oncogene. 2007;26:1297–305.

    Article  CAS  PubMed  Google Scholar 

  5. Zawilinska B, Kosinska A, Lenart M, Kopec J, Piatkowska-Jakubas B, Skotnicki A, et al. Detection of specific lytic and latent transcripts can help to predict the status of Epstein-Barr virus infection in transplant recipients with high virus load. Acta Biochim Pol. 2008;55:693–9.

    CAS  PubMed  Google Scholar 

  6. Gottschalk S, Rooney CM, Heslop HE. Post-transplant lymphoproliferative disorders. Annu Rev Med. 2005;56:29–44.

    Article  CAS  PubMed  Google Scholar 

  7. Kuppers R. B cells under influence: transformation of B cells by Epstein-Barr virus. Nat Rev Immunol. 2003;3:801–12.

    Article  PubMed  Google Scholar 

  8. Niller HH, Salamon D, Ilg K, Koroknai A, Banati F, Bauml G, et al. The in vivo binding site for oncoprotein c-Myc in the promoter for Epstein-Barr virus (EBV) encoding RNA (EBER) 1 suggests a specific role for EBV in lymphomagenesis. Med Sci Monit. 2003;9:HY1–9.

    CAS  PubMed  Google Scholar 

  9. Webber SA, Naftel DC, Fricker FJ, Olesnevich P, Blume ED, Addonizio L, et al. Lymphoproliferative disorders after paediatric heart transplantation: a multi-institutional study. Lancet. 2006;367:233–9.

    Article  PubMed  Google Scholar 

  10. Schubert S, Abdul-Khaliq H, Lehmkuhl HB, Yegitbasi M, Reinke P, Kebelmann-Betzig C, et al. Diagnosis and treatment of post-transplantation lymphoproliferative disorder in pediatric heart transplant patients. Pediatr Transplant. 2009;13:54–62.

    Article  CAS  PubMed  Google Scholar 

  11. Ohga S, Nomura A, Takada H, Hara T. Immunological aspects of Epstein-Barr virus infection. Crit Rev Oncol Hematol. 2002;44:203–15.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Draoua HY, Tsao L, Mancini DM, Addonizio LJ, Bhagat G, Alobeid B. T-cell post-transplantation lymphoproliferative disorders after cardiac transplantation: a single institutional experience. Br J Haematol. 2004;127:429–32.

    Article  CAS  PubMed  Google Scholar 

  14. Lundell R, Elenitoba-Johnson KS, Lim MS. T-cell posttransplant lymphoproliferative disorder occurring in a pediatric solid-organ transplant patient. Am J Surg Pathol. 2004;28:967–73.

    Article  PubMed  Google Scholar 

  15. Yang F, Li Y, Braylan R, Hunger SP, Yang LJ. Pediatric T-cell post-transplant lymphoproliferative disorder after solid organ transplantation. Pediatr Blood Cancer. 2008;50:415–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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;16:2052–9.

    Article  CAS  PubMed  Google Scholar 

  17. Dotti G, Fiocchi R, Motta T, Gamba A, Gotti E, Gridelli B, et al. Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant. Transplantation. 2000;69:827–33.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  19. Taylor AL, Marcus R, Bradley JA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit Rev Oncol Hematol. 2005;56:155–67.

    Article  PubMed  Google Scholar 

  20. Ross M, Kouretas P, Gamberg P, Miller J, Burge M, Reitz B, et al. Ten- and 20-year survivors of pediatric orthotopic heart transplantation. J Heart Lung Transplant. 2006;25:261–70.

    Article  PubMed  Google Scholar 

  21. Gao SZ, Chaparro SV, Perlroth M, Montoya JG, Miller JL, DiMiceli S, et al. Post-transplantation lymphoproliferative disease in heart and heart-lung transplant recipients: 30-year experience at Stanford University. J Heart Lung Transplant. 2003;22:505–14.

    Article  PubMed  Google Scholar 

  22. Green M, Bueno J, Rowe D, Mazariegos G, Qu L, Abu-Almagd K, et al. Predictive negative value of persistent low Epstein-Barr virus viral load after intestinal transplantation in children. Transplantation. 2000;70:593–6.

    Article  CAS  PubMed  Google Scholar 

  23. Lee TC, Savoldo B, Rooney CM, Heslop HE, Gee AP, Caldwell Y, et al. Quantitative EBV viral loads and immunosuppression alterations can decrease PTLD incidence in pediatric liver transplant recipients. Am J Transplant. 2005;5:2222–8.

    Article  PubMed  Google Scholar 

  24. Schubert S, Renner C, Hammer M, Abdul-Khaliq H, Lehmkuhl HB, Berger F, et al. Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients. J Heart Lung Transplant. 2008;27:100–5.

    Article  PubMed  Google Scholar 

  25. Allen UD, Farkas G, Hebert D, Weitzman S, Stephens D, Petric M, et al. Risk factors for post-transplant lymphoproliferative disorder in pediatric patients: a case-control study. Pediatr Transplant. 2005;9:450–5.

    Article  PubMed  Google Scholar 

  26. Bingler MA, Feingold B, Miller SA, Quivers E, Michaels MG, Green M, et al. Chronic high Epstein-Barr viral load state and risk for late-onset posttransplant lymphoproliferative disease/lymphoma in children. Am J Transplant. 2008;8:442–5.

    Article  CAS  PubMed  Google Scholar 

  27. Scheenstra R, Verschuuren EA, de Haan A, Slooff MJ, The TH, Bijleveld CM, et al. The value of prospective monitoring of Epstein-Barr virus DNA in blood samples of pediatric liver transplant recipients. Transpl Infect Dis. 2004;6:15–22.

    Article  CAS  PubMed  Google Scholar 

  28. Axelrod DA, Holmes R, Thomas SE, Magee JC. Limitations of EBV-PCR monitoring to detect EBV associated post-transplant lymphoproliferative disorder. Pediatr Transplant. 2003;7:223–7.

    Article  PubMed  Google Scholar 

  29. Swinnen LJ, Costanzo-Nordin MR, Fisher SG, O’Sullivan EJ, Johnson MR, Heroux AL, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med. 1990;323:1723–8.

    Article  CAS  PubMed  Google Scholar 

  30. Quintini C, Kato T, Gaynor JJ, Ueno T, Selvaggi G, Gordon P, et al. Analysis of risk factors for the development of posttransplant lymphoprolipherative disorder among 119 children who received primary intestinal transplants at a single center. Transplant Proc. 2006;38:1755–8.

    Article  CAS  PubMed  Google Scholar 

  31. Cox KL, Lawrence-Miyasaki LS, Garcia-Kennedy R, Lennette ET, Martinez OM, Krams SM, et al. An increased incidence of Epstein-Barr virus infection and lymphoproliferative disorder in young children on FK506 after liver transplantation. Transplantation. 1995;59:524–9.

    Article  CAS  PubMed  Google Scholar 

  32. Cao S, Cox KL, Berquist W, Hayashi M, Concepcion W, Hammes GB, et al. Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus. Pediatr Transplant. 1999;3:22–6.

    Article  CAS  PubMed  Google Scholar 

  33. Younes BS, McDiarmid SV, Martin MG, Vargas JH, Goss JA, Busuttil RW, et al. The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric liver transplant patients. Transplantation. 2000;70:94–9.

    CAS  PubMed  Google Scholar 

  34. Dharnidharka VR, Ho PL, Stablein DM, Harmon WE, Tejani AH. Mycophenolate, tacrolimus and post-transplant lymphoproliferative disorder: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant. 2002;6:396–9.

    Article  CAS  PubMed  Google Scholar 

  35. 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;80:1233–43.

    Article  CAS  PubMed  Google Scholar 

  36. Kahan BD, Yakupoglu YK, Schoenberg L, Knight RJ, Katz SM, Lai D, et al. Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients. Transplantation. 2005;80:749–58.

    Article  CAS  PubMed  Google Scholar 

  37. 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. Proc Natl Acad Sci USA. 2000;97:4285–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Majewski M, Korecka M, Joergensen J, Fields L, Kossev P, Schuler W, et al. Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation. 2003;75:1710–7.

    Article  CAS  PubMed  Google Scholar 

  39. Falco DA, Nepomuceno RR, Krams SM, Lee PP, Davis MM, Salvatierra O, et al. Identification of Epstein-Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients. Transplantation. 2002;74:501–10.

    Article  CAS  PubMed  Google Scholar 

  40. Kuzushima K, Hayashi N, Kudoh A, Akatsuka Y, Tsujimura K, Morishima Y, et al. Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8+ T cells. Blood. 2003;101:1460–8.

    Article  CAS  PubMed  Google Scholar 

  41. Annels NE, Kalpoe JS, Bredius RG, Claas EC, Kroes AC, Hislop AD, et al. Management of Epstein-Barr virus (EBV) reactivation after allogeneic stem cell transplantation by simultaneous analysis of EBV DNA load and EBV-specific T cell reconstitution. Clin Infect Dis. 2006;42:1743–8.

    Article  CAS  PubMed  Google Scholar 

  42. 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;80:595–9.

    Article  CAS  PubMed  Google Scholar 

  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;82:1093–100.

    Article  CAS  PubMed  Google Scholar 

  44. Bakker NA, van Imhoff GW, Verschuuren EA, van Son WJ. Presentation and early detection of post-transplant lymphoproliferative disorder after solid organ transplantation. Transpl Int. 2007;20:207–18.

    Article  CAS  PubMed  Google Scholar 

  45. Swerdlow SH, Webber SA, Chadburn A, Ferry JA, editors. Post-transplant lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL, et al, editors. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2008.

  46. Lones MA, Mishalani S, Shintaku IP, Weiss LM, Nichols WS, Said JW. Changes in tonsils and adenoids in children with posttransplant lymphoproliferative disorder: report of three cases with early involvement of Waldeyer’s ring. Hum Pathol. 1995;26:525–30.

    Article  CAS  PubMed  Google Scholar 

  47. Benkerrou M, Durandy A, Fischer A. Therapy for transplant-related lymphoproliferative diseases. Hematol Oncol Clin North Am. 1993;7:467–75.

    CAS  PubMed  Google Scholar 

  48. Cacciarelli TV, Green M, Jaffe R, Mazariegos GV, Jain A, Fung JJ, et al. Management of posttransplant lymphoproliferative disease in pediatric liver transplant recipients receiving primary tacrolimus (FK506) therapy. Transplantation. 1998;66:1047–52.

    Article  CAS  PubMed  Google Scholar 

  49. Newell KA, Alonso EM, Whitington PF, Bruce DS, Millis JM, Piper JB, et al. Posttransplant lymphoproliferative disease in pediatric liver transplantation. Interplay between primary Epstein-Barr virus infection and immunosuppression. Transplantation. 1996;62:370–5.

    Article  CAS  PubMed  Google Scholar 

  50. Dharnidharka VR, Douglas VK, Hunger SP, Fennell RS. Hodgkin’s lymphoma after post-transplant lymphoproliferative disease in a renal transplant recipient. Pediatr Transplant. 2004;8:87–90.

    Article  PubMed  Google Scholar 

  51. Gheorghe G, Albano EA, Porter CC, McGavran L, Wei Q, Meltesen L, et al. Posttransplant Hodgkin lymphoma preceded by polymorphic posttransplant lymphoproliferative disorder: report of a pediatric case and review of the literature. J Pediatr Hematol Oncol. 2007;29:112–6.

    Article  PubMed  Google Scholar 

  52. Dharnidharka VR, Douglas-Nikitin V. Hodgkin’s-like PTLD versus true Hodgkin’s disease. Pediatr Transplant. 2004;8:581–2.

    Article  PubMed  Google Scholar 

  53. Sculerati N, Arriaga M. Otolaryngologic management of posttransplant lymphoproliferative disease in children. Ann Otol Rhinol Laryngol. 1990;99:445–50.

    Article  CAS  PubMed  Google Scholar 

  54. Zangwill SD, Hsu DT, Kichuk MR, Garvin JH, Stolar CJ, Haddad J Jr, et al. Incidence and outcome of primary Epstein-Barr virus infection and lymphoproliferative disease in pediatric heart transplant recipients. J Heart Lung Transplant. 1998;17:1161–6.

    CAS  PubMed  Google Scholar 

  55. Tai CC, Curtis JL, Szmuszkovicz JR, Horn MV, Ford HR, Woo MS, et al. Abdominal involvement in pediatric heart and lung transplant recipients with posttransplant lymphoproliferative disease increases the risk of mortality. J Pediatr Surg. 2008;43:2174–7.

    Article  PubMed  Google Scholar 

  56. Gross TG, Bucuvalas JC, Park JR, Greiner TC, Hinrich SH, Kaufman SS, et al. Low-dose chemotherapy for Epstein-Barr virus-positive post-transplantation lymphoproliferative disease in children after solid organ transplantation. J Clin Oncol. 2005;23:6481–8.

    Article  CAS  PubMed  Google Scholar 

  57. Addonizio LJ, Boyle GJ, editors. Posttransplant malignancy: risk, factors, incidence, diagnosis, treatment. In: Canter CE, Kirklin JK, editors. Pediatric heart transplantation, vol. 2. Philadelphia: Elsevier; 2007.

  58. Kawa K, Sawada A, Koyama M, Inoue M. Epstein-Barr virus infection after unrelated cord blood transplantation: reactivation or reinfection? Int J Hematol. 2007;85:267–9.

    Article  PubMed  Google Scholar 

  59. Quintanilla-Martinez L, Kumar S, Fend F, Reyes E, Teruya-Feldstein J, Kingma DW, et al. Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood. 2000;96:443–51.

    CAS  PubMed  Google Scholar 

  60. Karras A, Thervet E, Legendre C. Hemophagocytic syndrome in renal transplant recipients: report of 17 cases and review of literature. Transplantation. 2004;77:238–43.

    Article  PubMed  Google Scholar 

  61. Awaya N, Adachi A, Mori T, Kamata H, Nakahara J, Yokoyama K, et al. Fulminant Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder with hemophagocytosis following autologous peripheral blood stem cell transplantation for relapsed angioimmunoblastic T-cell lymphoma. Leuk Res. 2006;30:1059–62.

    Article  CAS  PubMed  Google Scholar 

  62. Chisuwa H, Hashikura Y, Nakazawa Y, Kamijo T, Nakazawa K, Nakayama J, et al. Fatal hemophagocytic syndrome after living-related liver transplantation: a report of two cases. Transplantation. 2001;72:1843–6.

    Article  CAS  PubMed  Google Scholar 

  63. Green M, Michaels MG, Webber SA, Rowe D, Reyes J. The management of Epstein-Barr virus associated post-transplant lymphoproliferative disorders in pediatric solid-organ transplant recipients. Pediatr Transplant. 1999;3:271–81.

    Article  CAS  PubMed  Google Scholar 

  64. Randhawa PS, Jaffe R, Demetris AJ, Nalesnik M, Starzl TE, Chen YY, et al. Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease. N Engl J Med. 1992;327:1710–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Delecluse HJ, Kremmer E, Rouault JP, Cour C, Bornkamm G, Berger F. The expression of Epstein-Barr virus latent proteins is related to the pathological features of post-transplant lymphoproliferative disorders. Am J Pathol. 1995;146:1113–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Walling DM, Andritsos LA, Etienne W, Payne DA, Aronson JF, Flaitz CM, et al. Molecular markers of clonality and identity in Epstein-Barr virus-associated B-cell lymphoproliferative disease. J Med Virol. 2004;74:94–101.

    Article  CAS  PubMed  Google Scholar 

  67. Mourad WA, Tulabah A, Al Sayed A, Raja M, Khafaga Y, El Gamal H, et al. The impact of the World Health Organization classification and clonality assessment of posttransplant lymphoproliferative disorders on disease management. Arch Pathol Lab Med. 2006;130:1649–53.

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  69. Murphy SB. Classification, staging and end results of treatment of childhood non-Hodgkin’s lymphomas: dissimilarities from lymphomas in adults. Semin Oncol. 1980;7:332–9.

    CAS  PubMed  Google Scholar 

  70. von Falck C, Maecker B, Schirg E, Boerner AR, Knapp WH, Klein C, et al. Post transplant lymphoproliferative disease in pediatric solid organ transplant patients: a possible role for [18F]-FDG-PET(/CT) in initial staging and therapy monitoring. Eur J Radiol. 2007;63:427–35.

    Article  Google Scholar 

  71. Bianchi E, Pascual M, Nicod M, Delaloye AB, Duchosal MA. Clinical usefulness of FDG-PET/CT scan imaging in the management of posttransplant lymphoproliferative disease. Transplantation. 2008;85:707–12.

    Article  PubMed  Google Scholar 

  72. Meehan SM, Domer P, Josephson M, Donoghue M, Sadhu A, Ho LT, et al. The clinical and pathologic implications of plasmacytic infiltrates in percutaneous renal allograft biopsies. Hum Pathol. 2001;32:205–15.

    Article  CAS  PubMed  Google Scholar 

  73. Pescovitz MD. The use of rituximab, anti-CD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant. 2004;8:9–21.

    Article  CAS  PubMed  Google Scholar 

  74. Ganne V, Siddiqi N, Kamaplath B, Chang CC, Cohen EP, Bresnahan BA, et al. Humanized anti-CD20 monoclonal antibody (Rituximab) treatment for post-transplant lymphoproliferative disorder. Clin Transplant. 2003;17:417–22.

    Article  PubMed  Google Scholar 

  75. 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;107:3053–7.

    Article  CAS  PubMed  Google Scholar 

  76. Blaes AH, Peterson BA, Bartlett N, Dunn DL, Morrison VA. Rituximab therapy is effective for posttransplant lymphoproliferative disorders after solid organ transplantation: results of a phase II trial. Cancer. 2005;104:1661–7.

    Article  CAS  PubMed  Google Scholar 

  77. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–42.

    Article  CAS  PubMed  Google Scholar 

  78. Mounier N, Briere J, Gisselbrecht C, Emile JF, Lederlin P, Sebban C, et al. Rituximab plus CHOP (R-CHOP) overcomes bcl-2-associated resistance to chemotherapy in elderly patients with diffuse large B-cell lymphoma (DLBCL). Blood. 2003;101:4279–84.

    Article  CAS  PubMed  Google Scholar 

  79. Trappe RU, Choquet S, Reinke P, Dreyling M, Mergenthaler HG, Jager U, et al. Salvage therapy for relapsed posttransplant lymphoproliferative disorders (PTLD) with a second progression of PTLD after Upfront chemotherapy: the role of single-agent rituximab. Transplantation. 2007;84:1708–12.

    Article  CAS  PubMed  Google Scholar 

  80. Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, et al. Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol. 2008;26:4587–94.

    Article  CAS  PubMed  Google Scholar 

  81. Orjuela M, Gross TG, Cheung YK, Alobeid B, Morris E, Cairo MS. A pilot study of chemoimmunotherapy (cyclophosphamide, prednisone, and rituximab) in patients with post-transplant lymphoproliferative disorder following solid organ transplantation. Clin Cancer Res. 2003;9:3945S–52S.

    CAS  PubMed  Google Scholar 

  82. 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;6:569–76.

    Article  CAS  PubMed  Google Scholar 

  83. Aalto SM, Juvonen E, Tarkkanen J, Volin L, Ruutu T, Mattila PS, et al. Lymphoproliferative disease after allogeneic stem cell transplantation—pre-emptive diagnosis by quantification of Epstein-Barr virus DNA in serum. J Clin Virol. 2003;28:275–83.

    Article  PubMed  Google Scholar 

  84. Funch DP, Walker AM, Schneider G, Ziyadeh NJ, Pescovitz MD. Ganciclovir and acyclovir reduce the risk of post-transplant lymphoproliferative disorder in renal transplant recipients. Am J Transplant. 2005;5:2894–900.

    Article  CAS  PubMed  Google Scholar 

  85. Hierro L, Diez-Dorado R, Diaz C, De la Vega A, Frauca E, Camarena C, et al. Efficacy and safety of valganciclovir in liver-transplanted children infected with Epstein-Barr virus. Liver Transpl. 2008;14:1185–93.

    Article  PubMed  Google Scholar 

  86. Green M, Reyes J, Webber S, Rowe D. The role of antiviral and immunoglobulin therapy in the prevention of Epstein-Barr virus infection and post-transplant lymphoproliferative disease following solid organ transplantation. Transpl Infect Dis. 2001;3:97–103.

    Article  CAS  PubMed  Google Scholar 

  87. 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;68:1517–25.

    Article  CAS  PubMed  Google Scholar 

  88. Davis CL. The antiviral prophylaxis of post-transplant lymphoproliferative disorder. Springer Semin Immunopathol. 1998;20:437–53.

    Article  CAS  PubMed  Google Scholar 

  89. Green M, Michaels MG, Katz BZ, Burroughs M, Gerber D, Shneider BL, et al. CMV-IVIG for prevention of Epstein Barr virus disease and posttransplant lymphoproliferative disease in pediatric liver transplant recipients. Am J Transplant. 2006;6:1906–12.

    Article  CAS  PubMed  Google Scholar 

  90. Humar A, Hebert D, Davies HD, Humar A, Stephens D, O’Doherty B, et al. A randomized trial of ganciclovir versus ganciclovir plus immune globulin for prophylaxis against Epstein-Barr virus related posttransplant lymphoproliferative disorder. Transplantation. 2006;81:856–61.

    Article  CAS  PubMed  Google Scholar 

  91. Birkeland SA, Andersen HK, Hamilton-Dutoit SJ. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol. Transplantation. 1999;67:1209–14.

    Article  CAS  PubMed  Google Scholar 

  92. Nepomuceno RR, Balatoni CE, Natkunam Y, Snow AL, Krams SM, Martinez OM. Rapamycin inhibits the interleukin 10 signal transduction pathway and the growth of Epstein Barr virus B-cell lymphomas. Cancer Res. 2003;63:4472–80.

    CAS  PubMed  Google Scholar 

  93. El-Salem M, Raghunath PN, Marzec M, Wlodarski P, Tsai D, Hsi E, et al. Constitutive activation of mTOR signaling pathway in post-transplant lymphoproliferative disorders. Lab Invest. 2007;87:29–39.

    Article  CAS  PubMed  Google Scholar 

  94. Pascual J. Post-transplant lymphoproliferative disorder—the potential of proliferation signal inhibitors. Nephrol Dial Transplant. 2007;22(Suppl 1):i27–35.

    Article  CAS  PubMed  Google Scholar 

  95. Sanchez-Brotons JA, Sobrino-Marquez JM, Lage-Galle E, Romero-Rodriguez N, Guisado A, Jimenez-Diaz J, et al. Preliminary experience with conversion from calcineurin inhibitors to everolimus in cardiac transplantation maintenance therapy. Transplant Proc. 2008;40:3046–8.

    Article  CAS  PubMed  Google Scholar 

  96. Zuckermann AO, Aliabadi AZ. Calcineurin-inhibitor minimization protocols in heart transplantation. Transpl Int. 2009;22:78–89.

    Article  CAS  PubMed  Google Scholar 

  97. Jimenez-Rivera C, Avitzur Y, Fecteau AH, Jones N, Grant D, Ng VL. Sirolimus for pediatric liver transplant recipients with post-transplant lymphoproliferative disease and hepatoblastoma. Pediatr Transplant. 2004;8:243–8.

    Article  CAS  PubMed  Google Scholar 

  98. Kusuki S, Hashii Y, Fukushima N, Takizawa S, Tokimasa S, Kogaki S, et al. Pediatric post-transplant diffuse large B cell lymphoma after cardiac transplantation. Int J Hematol. 2009;89:209–13.

    Article  PubMed  Google Scholar 

  99. Posfay-Barbe KM, Siegrist CA. Immunization and transplantation–what is new and what is coming? Pediatr Transplant. 2009;13:404–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Ayumi Furumoto for providing pathology photomicrograph and Dr. Emiko Sato for critically reading the manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hideaki Ohta & Keiichi Ozono

  2. Department of Transplantation Medicine, Osaka University Hospital, Osaka, Japan

    Norihide Fukushima

Authors
  1. Hideaki Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Norihide Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keiichi Ozono
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideaki Ohta.

About this article

Cite this article

Ohta, H., Fukushima, N. & Ozono, K. Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation. Int J Hematol 90, 127–136 (2009). https://doi.org/10.1007/s12185-009-0399-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-009-0399-x

Keywords

Search

Navigation