RITUXIMAB WITH PLASMAPHERESIS AND SPLENECTOMY IN ABO-INCOMPATIBLE LIVER TRANSPLANTATION (2003)

Plasmapheresis (PP) with or without splenectomy prevents hyperacute rejection (HAR) after ABO-incompatible (ABO-I) liver transplants in small children, but the efficacy of such therapy in larger children and adults is unproved (1, 2). We report the successful addition of rituximab, a chimeric CD20 monoclonal antibody, to PP and splenectomy to prevent HAR of an ABO-I liver graft. A 15-year-old boy (62 kg) presented with fulminant hepatic failure of unknown origin. Increased intracranial pressure, onset of decerebrate posture, and lack of availability of other livers led to transplantation of an ABO-I (A donor → O recipient) liver. He underwent PP immediately before the transplantation and on days 1, 3, 4, 6, 8, and 10 after the transplantation with AB donor plasma. Splenectomy was performed after graft perfusion followed by infusion of 375 mg/m2 of rituximab. Basiliximab (20 mg) was administered after graft perfusion and on day 4. Routine immunosuppression consisted of tacrolimus, mycophenolate, and steroids. Intravenous ganciclovir and cytomegalovirus-specific immune globulin were administered for the first 3 months. Initial anti-A isoagglutinin titers were 1:32 and peaked at 1:128 on day 2 and remained below 1:64 throughout the first 10 postoperative days. Lymphocyte markers in the peripheral blood are shown in Table 1. An episode of rejection on day 22 responded to steroids. He developed severe anemia and thrombocytopenia 5 weeks after transplantation. Bone marrow biopsy showed hypocellularity, and reticulocyte counts ranged between 0.8 and 1.5%. Parvovirus B19 serologies were negative. He required red cell transfusions for 11 months and platelets for 17 months after the transplantation. He did not have any other complications. Currently, 30 months after transplantation, the patient’s liver chemistries, white blood count, and hemoglobin are normal. The platelet count varies around 70,000/mm3.Table 1: Flow cytometry of various B-cell markers in the peripheral blood (expressed as percent of cells scanned) before and after liver transplantationTo our knowledge this is the first report of using rituximab with PP and splenectomy in preventing HAR after ABO-I liver transplantation. The literature indicates our patient had a 75% risk of graft loss with PP alone (2). Addition of splenectomy to PP improves 1-year graft survival in ABO-I kidney transplants from 33 to 81% (3). With lack of sufficient data indicating that the combination of splenectomy with PP would eliminate the risk of HAR in older children and adults, we added rituximab to further increase the margin of success (1). A single dose of rituximab with splenectomy was effective in depleting B cells for up to 25 days after transplantation. Given that rituximab can be administered in more than one dose, it is possible that the use of rituximab may decrease the need for splenectomy in these extremely ill patients. Although disseminated cytomegalovirus infection and parvovirus B19 infections have been reported after the use of rituximab, our patient did not develop any serious infections (4, 5). The exact cause of the aplastic anemia in our patient is unknown; it could be a direct toxic effect of rituximab or caused by parvovirus B19 infection despite lack of serologic response. The efficacy and safety of rituximab combined with PP and splenectomy in patients receiving ABO-I liver transplants needs further corroboration. Iona Monteiro Lucille M. McLoughlin Adrian Fisher Andrew N. de la Torre Baburao Koneru