It is more difficult to control humoral rejection in living donor liver transplantations (LDLT) across the ABO blood group barrier than in matched or compatible combinations. We achieved excellent results in ABO-incompatible transplantation with novel immunosuppressive regimens and plasma exchange (PE). Among 82 LDLT were 10 cases of ABO-incompatible recipients, including three who were administered rituximab for rescue or prophylactic therapy. Pretransplantation PE was performed as necessary to maintain hemagglutinin titers below 1:16 and posttransplantation PE was performed when there were signs of hyperacute rejection associated with high titers. Induction immunosuppression consisted of FK506, steroid, mycophenolate mofetil (MMF), and rituximab. The first patient was administered rituximab with deoxyspergualin (DSG), steroid pulse therapy, and PE on postoperative day (POD) 7, because of biopsy-proven humoral acute rejection. The titers and LFTs improved drastically. The second and third patients were administered rituximab just after the operation with other routine immunosuppressants for prophylaxis of hyperacute rejection. The second patient showed a slight deterioration in LFTs with an elevated titer, which normalized after steroid pulse therapy and PE. The third patient had no episodes of rejection. At present, that is 27, 17, and 6 months after the operations respectively, the 3 transplant recipients are in stable condition.
"In most clinical studies, two main strategies to reduce antibody-mediated complications have been tested in combination . First, preformed isoagglutinins in the recipient are reduced before transplantation by apheresis    or immunoadsorption   . Second, restoration of isoagglutinins by plasma cells is suppressed by splenectomy, reinforced immunosuppression , or by specifically interfering with the maturation [17, 21, 25–28] or activation   of B cells. "
[Show abstract][Hide abstract] ABSTRACT: Adult living donor liver transplantations (ALDLTs) across the ABO blood group barrier have been reported in Asia, North Americas, and Europe, but not yet in Germany. Several strategies have been established to overcome the detrimental effects that are attached with such a disparity between donor and host, but no gold standard has yet emerged. Here, we present the first experiences with three ABO-incompatible adult living donor liver transplantations in Germany applying different immunosuppressive strategies. Four patient-donor couples were considered for ABO-incompatible ALDLT. In these patients, resident ABO blood group antibodies (isoagglutinins) were depleted by plasmapheresis or immunoadsorption and replenishment was inhibited by splenectomy and/or B-cell-targeted immunosuppression. Despite different treatments ALDLT could safely be performed in three patients and all patients had good initial graft function without signs for antibody-mediated rejection (AMR). Two patients had long-term graft survival with stable graft function. We thus propose the feasibility of ABO-incompatible ALDLT with these protocols and advocate further expansion of ABO incompatible ALDLT in multicenter trials to improve efficacy and safety.
Journal of Transplantation 01/2009; 2009:759581. DOI:10.1155/2009/759581
[Show abstract][Hide abstract] ABSTRACT: Purpose of review: Much attention has recently been placed on transplanting anti-Human Leukocyte Antigen (HLA) sensitized patients and using ABO-incompatible organs. To achieve this goal, the antibodies must be removed. It is therefore timely to provide a review that updates the current literature on drugs and modalities being used including intravenous immunoglobulin-G, mycophenolate mofetil, sirolimus, Campath, Protein A immunoabsorption, and rituximab.
Recent findings: The most important recent study, a randomized trial of intravenous immunoglobulin-G versus placebo, confirmed the efficacy of intravenous immunoglobulin-G for desensitization. Campath appears to be unable to prevent antibody-mediated rejection and therefore is probably not suitable for desensitization. Animal data suggest that immunoabsorption columns might be working through the systemic exposure of Protein A. Rituximab, a B-cell specific antibody, appears to be safe and to have some efficacy as a sole agent in elimination of alloantibodies but most likely will require combination therapy. Newer agents such as humanized anti-CD20 and drugs targeting other B-cell antigens such as BAFF (B-cell Activation Factor of the TNF Family) and APRIL (A PRoliferation-Inducing Ligand) are being developed.
Summary: Although many reports are appearing that demonstrate successful transplants, there is a major deficiency in controlled clinical trials with these drugs. Focus over the near future should be to prove the efficacy through the use of randomized trials.
Current Opinion in Organ Transplantation 11/2005; 10(4):279-283. DOI:10.1097/01.mot.0000183248.12710.16 · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rituximab, chimeric anti-human CD20, is approved for treatment of B-cell lymphoma in adults. It is being used experimentally in other various immune-related diseases such as immune thrombocytopenic purpura, systemic lupus erythematosus, myasthenia gravis and rheumatoid arthritis. In transplant recipients, it is used for treatment of post-transplant lymphoproliferative disease, to anecdotally reduce pre-formed anti-HLA and anti-ABO antibodies and for the prevention and treatment of acute rejection. This article primarily reviews the science behind rituximab: its history, pharmacokinetics and potential mechanism of action. A need for controlled clinical trials is clearly indicated before the widespread use of this drug in transplant.
American Journal of Transplantation 06/2006; 6(5 Pt 1):859-66. DOI:10.1111/j.1600-6143.2006.01288.x · 5.68 Impact Factor
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