Abstract
Background: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after organ transplantation associated with a high mortality, and is often caused by a primary or reactivated Epstein-Barr virus (EBV) infection. The incidence of PTLD ranges from 1% to 10%, depending on the type of organ transplanted and the immunosuppressive regimens used.
Methods: In this retrospective study from a single center, 12 (2.4%) of 500 consecutive recipients of liver grafts developed lymphoma. Patient data were obtained by chart review. All diagnostic biopsies were reviewed by two hematopathologists.
Results: The median time between transplantation and the diagnosis of lymphoma was 19.5 (1.5–148) mo. Nine of the patients had been treated with OKT-3 and/or ATG after the transplantation. Two patients had a pretransplant diagnosis of lymphoma. The PTLD was of high grade in all patients, and was associated with EBV in 6 of 9 examined cases. No relation with human herpesvirus-8 could be detected. In all patients, immuno-suppression was reduced at the time of lymphoma diagnosis. Chemotherapy was used in all patients, mostly upfront but in one patient after lymphoma progression after reduction of immunosuppression. Nine patients also got antiviral therapy. Immunotherapy with the monoclonal antibody rituximab was used in one patient. Half of the patients are alive, in complete continuous remission, more than 4 yr after the lymphoma diagnosis. Two patients died of neutropenic sepsis, three of persistent lymphoma, and one of recurrent cirrhosis while in complete remission.
Conclusions: PTLD is a significant complication in liver-transplanted patients. Intensive chemotherapy can induce long-term remissions in a substantial number of patients. The role for monoclonal antibodies in this setting should be investigated further.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Penn I. The changing pattern of posttransplant malignancies. Transpl Proc 1991; 23:1101–1103.
Armitage JM, et al. Posttransplant lymphoproliferative disease in thoracic organ transplant patients: ten years of cyclosporine-based immunosuppression. J Heart Lung Transplant 1991; 10:877–887.
Sheil AGR. Cancer in immune-suppressed organ transplant recipients: aetiology and evolution. Transplant Proc 1998; 30:2055–2057.
Praghakaran K, Wise B, Chen A, Schwarz K, Colombani P. Rational management of posttransplant lymphoproliferative disorder in pediatric patients. J Pediatr Surg 1999; 34:112–116.
Ho M, et al. Epstein-Barr virus infections and DNA hybridization studies in post-transplant lymphomas and lymfoproliferative lesions: the role of primary infection. J Infect Dis 1985; 152:876–886.
Haque T, Crawford DH. Role of adoptive immunotherapy in the prevention and treatment of lymphoproliferative disease following transplantation. Br J Haematol 1999; 106:309–316.
Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI. Aggressive treatment for post-cardiac transplant lymphoproliferation. Blood 1995; 86:3333–3340.
Coiffier B, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346:235–242.
Dotti G, et al. Anti-CD20 antibody (rituximab) administration in patients with late-occurring lymphomas after solid organ transplant. Haematologica 2001; 86:618–623.
Zompi S, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with clonal lymphoproliferative disorders after orthotopic liver transplantation: a report of three cases. J Hepatol 2000; 32:521–527.
Rooney CM, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogenic transplant recipients. Blood 1998; 92:1549–1555.
Haque T, et al. Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells. Transplantation 2001; 72:1399–1402.
Khanna R, et al. Activation and adoptive transfer of Epstein-Barr virus-specific cytotoxic T cells in solid organ transplant patients with posttransplant lymphoproliferative disease. Proc Natl Acad Sci USA 1999; 96:10391–10396.
Harris NL, Swerdlow SH, Frizzera G, Knowles DM. Post-transplant lymphoproliferative disorders. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) WHO Classification. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2001, pp. 264–269.
Gerstenkorn C, Jackson G, Di Franco F, Thomusch O, Talbot D. Outcome of PTLD in renal and liver allograft recipients. Transplant Proc 2001; 33:2469–2472.
Glez-Chamorro A, et al. Management and outcome of liver recipients with post-transplant lymphoproliferative disease. Hepato-Gastroenterology 2000; 47:211–219.
Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993; 342:1514–1516.
Swinnen LJ, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med 1990; 323:1723–1728.
Saigal S, et al. Successful outcome of orthotopic liver transplantation in patients with preexisting malignant states. Liver Transplantation 2001; 7:11–15.
Romero R, et al. Simultaneous kidney-pancreas transplantation in patient with small lymphocytic lymphoma. Transplantation 2003; 75:414–416.
Dotti G, et al. Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney and liver transplant. Transplantation 2000; 69:827–833.
Kapelushnik J, et al. Post renal transplantation human herpesvirus 8-associated lymphoproliferative disorder and Kaposi’s sarcoma. Br J Haematol 2001; 113:425–428.
Muti G, et al. Post-transplant lymphoproliferative disorders: improved outcome after clinico-pathologically tailored treatment. Hematologica 2002; 87:67–77.
Caillard S, Lachat V, Moulin B. Posttransplant lymphoproliferative disorders in allograft recipients: report of 53 cases of a French multicenter study. Transpl Int 2000; 13[Suppl 1]:S388-S393.
Penn I, Hammond W, Brettschneider L. Starzl TE. Malignant lymphomas in transplantation patients. Transplant Proc 1969; 1:106–111.
Tsai DE, 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; 71:1076–1088.
Davis CL. Interferon and cytotoxic chemotherapy for the treatment of post-transplant lymphoproliferative disorder. Transpl Inf Dis 2001; 3:108–118.
Milpied N, et al. Humanized anti-CD20 monoclonal antibody (Rituximab) in post-transplant B-lymphoproliferative disorder: a retrospective analysis of 32 patients. Ann Oncol 2000: 11[Suppl 1]: S113-S116.
Mentzer SJ, Perinne SP, Faller DV. Epstein-Barr virus post-transplant lymphoproliferative disease and virus-specific therapy: pharmacological re-activation of viral target genes with arginine butyrate. Transpl Infect Dis 2001; 3:177–185.
Mamzer-Bruneel M-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; 18:3622–3632.
Muti G, et al. Incidence and clinical characteristics of posttransplant lymphoproliferative disorders: report from a single center. Transplant Int 2000; 13[Suppl 1]: S382-S387.
Comoli P, et al. Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 2002; 99:2592–2598.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Norin, S., Kimby, E., Ericzon, BG. et al. Posttransplant lymphoma—A single-center experience of 500 liver transplantations. Med Oncol 21, 273–284 (2004). https://doi.org/10.1385/MO:21:3:273
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MO:21:3:273