The Role of Immunosuppression in Lymphoma
Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients and currently represents the second most common de novo malignancy following solid organ transplantation. PTLD has been
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Abstract Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients and currently represents the second most common de novo malignancy following solid organ transplantation. PTLD has been noted in all transplant immunosuppressive eras including the pre-cyclosporine, cyclosporine, and post-cyclosporine eras. The time from organ transplantation to PTLD presentation varies widely from less than 1 month to several years. PTLD presents with a broad spectrum of clinical manifestations depending on the transplanted organ, immunosuppressive therapy and patient age. Intense immunosuppressive therapy is a major risk factor for development of PTLD. Whenever a new agent is introduced, there is a learning curve that leads to dosing modifications, which in turn result in optimization of its immunosuppressive efficacy and reduction of toxicities, including PTLD. We review the major historical and recent immunosuppression trials to assess the impact of individual immunosuppressive agents and regimens on PTLD risk.
Introduction Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized yet serious complication in solid organ transplant recipients. It represents the second most common de novo malignancy following transplantation (Penn 2000) and manifests as a wide spectrum of Epstein-Barr virus (EBV)-related disease, ranging from benign hyperplasia to frank malignancies (Penn 2000). PTLD presents with a Recent Results in Cancer Research, Vol. 159 ° Springer-Verlag Berlin Heidelberg 2002
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broad spectrum of clinical scenarios depending on the transplanted organ, immunosuppressive therapy and the age of the patient. PTLD was recognized three decades ago by Starzl and Penn (Denver, Colorado, 1968) in two patients who presented with gastrointestinal and neurologic non-Hodgkin's lymphoma (Penn 1969). Penn and colleagues reported these and three other cases of lymphoma from other transplant centers (Minneapolis and Edinburgh, Scotland) in 1969 (Penn 1969). All five cases occurred in living related-kidney transplant recipients, and all received azathioprine and prednisone as maintenance immunosuppression. Additionally antilymphocyte globulin (ALG) was administered in three cases. Four of the five patients died from lymphoma (Penn 1969). Following this report, Israel Penn established a transplant tumor registry in 1969, first at Denver, which later relocated with him to Cincinnati. Now known as the Israel Penn International Transplant Tumor Registry (IPITTR), it represents the only worldwide repository of neoplastic complications in transplant recipients. The IPITTR maintains data on recipients with: (1) a pre-transplant history of cancer, (2) post-transplant de novo tumors, (3) post-transplant recurrent tumors and (4) donor-derived tumors. As of January 1999, the registry has collected data on 14,373 cancers involving 13,500 organ transplant recipients. Various reports and the IPITTR have shown the incidence of PTLD to vary accor
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