Diagnosis and treatment of transplant-related lymphoma

Immunodeficiency-related B-cell disorders are seen after organ transplantat ion and ill congenital and acquired immunodeficiency states. Post-transplan t lymphoproliferative disorders (PTLD) comprise a histologic spectrum rangi ng from hyperplastic appearing lesions to frank non-Hodgkin's lymphoma or m ultiple myeloma histology. Multiple clones may co-exist, representing a uni quely different mechanism for lymphomagenesis. The incidence varies from 1% in renal recipients to 8% in lung recipients, but can be markedly increase d by the use of anti-T-cell therapies, or by T-cell depletion in bone marro w transplantation. Pre-transplant EBV seronegativity increases risk to as h igh as 30%-50%. More than 90% of tumors are EBV-associated. Mechanisms for viral lymphomagenesis remain incompletely defined; LMP-1 may function as an oncogene and coprecipitates with TRAF, BCL-2 overexpression has also been identified. A possible direct tumorigenic effect has recently been suggeste d fur cyclosporine. PTLD has a highly variable clinical picture, certain pa tterns are however seen. Reversibility of PTLD with reduction in immunosupp ressives has long been recognized. Predicting reversibility has been diffic ult. The presence or absence of BCL-6 mutations has recently been identifie d as being of predictive value. Surgical resection can be curative. Cytotox ics, although problematic. can also be curative. Long term remission has be en achieved with anti CD21 and CD24 antibodies: efficacy has been reported anecdotally for interferon alpha and for rituximab. In vitro expanded EBV-s pecific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood ap pears to correlate with the emergence of PTLD and may facilitate prophylact ic studies. PTLD is a model of immunodeficiency related EBV lymphomagenesis. Pathogenet ic, therapeutic, and prophylactic insights gained from the study of PTLD ar e likely to be applicable to other immunodeficiency states and to EBV-relat ed lymphoid neoplasia in general.