Search

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after organ transplantation with a cumulative incidence of 1.1% at 18 months and 4.7% at 15 years. It has been reported in patients with or without concomitant Epstein-Barr virus infection. Therapy ranges from a reduction of immunosuppression to administration of conventional cytotoxic chemotherapy. Rituximab, a recombinant chimeric anti-CD20 monoclonal antibody has been used for the treatment of PTLD with promising results and a reduction in treatment-associated mortality. However, the use of rituximab has been associated with spontaneous gastrointestinal perforation. We describe a case of recurrent intestinal perforations after a single dose of rituximab.

Costimulatory blockade with anti-CD154 monoclonal antibody (aCD154) prolongs allograft survival in nonhuman primates, but has not reliably induced tolerance when used alone. In the current studies, we evaluated the effect of adding CD154 blockade to a chimerism inducing nonmyeloablative regimen in primates. We observed a significant improvement of donor bone marrow (DBM) engraftment, which has been associated with a lower incidence of acute rejection and long-term survival of renal allografts without the need for previously required splenectomy. Among the long-term survivors, four never showed evidence of rejection, with the longest survival exceeding 1700 days following discontinuation of immunosuppression. Nevertheless, late chronic rejection was observed in three of eight recipients, indicating the necessity of further modifications of the regimen. Control recipients receiving no DBM or donor splenocytes in place of DBM rejected their allografts. Thus, DBM engraftment with, at least, transient mixed chimerism appears essential for induction of allograft tolerance using this conditioning regimen. Modification of the original mixed chimerism approach, by the addition of costimulatory blockade, has been shown to enhance mixed chimerism and induce renal allograft tolerance with less morbidity in nonhuman primates.