Post-transplant lymphoproliferative disorder--the potential of proliferation signal inhibitors

Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of diseases characterized by abnormal lymphoid proliferation following transplantation. These lymphomas, in particular, have been shown to have a higher incidence in renal transplant recipients compared with the general age-matched population. The effect of different immunosuppressive regimens on the incidence of PTLD has been assessed in a number of studies. Although there are conflicting data on the role of calcineurin inhibitors (CNIs) in promoting the development of PTLD, an increase in risk is described in most studies and is usually related to the aggressiveness of immunosuppression. The proliferation signal inhibitors (PSIs), everolimus and sirolimus, have both immunosuppressive and antiproliferative actions and pre-clinical data suggest that everolimus has an inhibitory effect on the growth of PTLD-derived cell lines. There is currently limited clinical data on the use of PSIs in the management of PTLD, therefore, clinical experience from nine European Transplant centres has been pooled and analysed to assess their potential. Conversion to PSIs and subsequent minimization or withdrawal of CNIs was analysed in 19 renal transplant recipients with PTLD and remission was observed in 15 patients. These data suggest that PSIs may assist with the management of PTLD following renal transplantation.