Post-transplant lymphoproliferative disorders in renal transplantation: two decades of experience

Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients of solid organs which seem to be related to Epstein Barr Virus (EBV). EBV seronegativity in the receptor, the use of antilymphocyte antibodies, acute rejection and CMV disease exist been identified as classical risk factors. We have studied the incidence of PTLD and its relationship with EBV in 1176 adult renal transplant recipients from cadaveric donors, who were transplanted in our hospital from 1988 to 2009. We have also evaluated the variation of PTLD incidence in 2 decades, the risk factors and the outcome of the patients who developed PTLD even with the new therapies. All patients received immunosuppression with calcineurin inhibitors, prednisone and azathioprine, switched to MMF since 1998. Immunological risk recipients were treated with antilymphocyte antibodies. PTLD was always diagnosed histologically and EBV determined in proliferative cells by hibridation in situ. Two different periods were analized:1988-1998 and 1999-2009 with 472 and 704 recipients respectively in each group.The follow-up was between 1 and 255 months. We identified 28 recipients, 22 males and 6 females, aged 18 to 70 years (mean age 46.5 +/- 15.3 years) with a time between grafting and PTLD of 72.9 +/- 56.3 months (1-180 months), who developed PTLD (2.3%). Ten patients CD20 positive were treated with rituximab. Thirteen of 28 recipients (46.4%) had no classical risk factor and only 4 patients had more than one. The presence of EBV in the lymphoproliferative cells was confirmed in 18 out of the 26 studied recipients (69.2%). Twenty-five out 28 proliferations were due to B lymphocytes (89.2%). The density incidence PTLD/year/patient was similar in both periods,0.003922 and 0,003995, respectively The patient survival after transplantation in the recipients who develop PTLD was 73,6% at 5 years and 36.9% at 10 years respectively against 87,8% and 75,9% in the patients without PTLD, p<0.0001. The graft survival was 62.6% at 5 years and 27.3% at 10 years while was 72.4% and 53.9% in the group of patients without PTLD. P<0.0001. The patient and graft survivals were 30.9% and 15.5% at 1 year; 23.2% and 7.7% at 2 years after the diagnosis of PTLD. There was no significant difference in the survival of patients treated with rituximab. Six out of 10 patients treated died, 5 of them due to the disease. In conclusion, PTLD is a disease with a poor prognosis in renal transplant patients. Most of the proliferations are due to B lymphocytes. It seems to have a close relationship between EBV and PTLD, which can develop in the absence of classical risk factors. The incidence of PTLD has not changed in the last two decades.