Epstein-Barr virus-negative lymphoproliferative disorders in long-term survivors after heart, kidney, and liver transplant

Background. Solid organ transplant patients undergoing long-term immunosupp ression have high risk of developing lymphomas. The pathogenesis of the lat e-occurring posttransplantation lymphoproliferative disorders ((PTLD) have not yet been extensively investigated, Methods. We studied 15 patients who developed PTLD after a median of 79 mon ths (range 22-156 months) after organ transplant, Clonality, presence of Ep stein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southe rn blot analysis or polymerase chain reaction. Results. All monomorphic PTLD and two of three polymorphic PTLD showed a mo noclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even l ower (31%). A c-myc gene rearrangement; was found in two cases (13%), where as none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement, The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EUV genom e, The clinical outcome after chemotherapy was poor because of infectious c omplications and resistant disease. With a median follow-up of 4 months, th e median survival time of these patients was 7 months. Conclusions. Late occurring lymphomas could be considered an entity distinc t from PTLD, occurring within 1 year of transplant, because they show a his tological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clona l, and may rearrange the c-myc oncogene. New therapeutic strategies ale req uired to reduce the mortality rate, and new modalities of long-lasting immu nosuppression are called for.