Post-transplant Lymphoproliferative Disorders: Implications for Acquired Immunodeficiency Syndrome-Associated Malignancies

Post-transplant lymphoproliferative disorders (PTLDs) comprisea histologic spectrum, ranging from hyperplastic-appearing lesionsto frank non-Hodgkin's lymphoma or multiple myeloma histology.Multiple clones may coexist, each representing a discrete lymphomagenicevent, a situation that is unique to immunodeficiency states.The incidence varies from 1% in renal recipients to 5% in heartrecipients, but can be markedly increased by the use of anti-T-celltherapies or by T-cell depletion in bone marrow transplantation.PTLD continues to arise, even many years after transplantation,and late T-cell lymphomas have recently been recognized. PretransplantEpstein-Barr virus (EBV) seronegativity increases risk to ashigh as 30%–50%. PTLD has a highly variable clinical picture;certain patterns are, however, seen. Reversibility of PTLD withreduction in immunosuppressives has long been recognized. Predictingreversibility has been difficult. The presence or absence ofbcl-6 mutations has recently been identified as being of predictivevalue. Surgical resection can be curative. Cytotoxics, althoughproblematic, can also be curative. Long-term remission has beenachieved with anti CD21 and CD24 antibodies; efficacy has beenreported for interferon alfa and for rituximab. In vitro expandedEBV-specific T cells have been effective as treatment and asprophylaxis in the setting of bone marrow transplantation. EBVviral load measured in blood appears to associate with the emergenceof PTLD and may facilitate prophylactic studies. PTLD is a modelof immunodeficiency-related EBV lymphomagenesis. Pathogenetic,therapeutic, and prophylactic insights gained from the studyof PTLD are likely to be applicable to the acquired immunodeficiencysyndrome setting.