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Swiss Medical Weekly ; 151(SUPPL 256):5S, 2021.
Article in English | EMBASE | ID: covidwho-1623110


Background: Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach in the clinical situation has been a combined kidney and hemato-poietic stem cell transplantation from the same living donor. Here, we report the first three patients included in this first European trial to induce tolerance by mixed lymphohematopoietic chimerism. Methods: The protocol followed previous studies at Stanford University: kidney transplantation was performed on day 0 including induction with anti-thymocyte globulin followed by conditioning with 10x1.2 Gy total lymphoid irradiation and the transfusion of CD34+ stem cells together with a body weight-adjusted dose of donor T cells. Immunosuppression consisted of cyclosporin and steroids for 10 days, cyclosporin and mycofenolate mofetil for 1 month, and then cyclosporin monotherapy with tapering over 9-20 months. Results: Two female and one male patients were transplanted with a kidney and peripherally mobilized hematopoietic stem cells from their HLA-identical sibling donor. No rejection or graft-versus-host disease occurred in these patients, which are currently off immunosuppression since 31, 18 and 6 months. Chimerism was stable in the first, but slowly declining in the other two patients. A molecular microscope analysis in patient 2 revealed the genetic profile of a normal kidney. No relevant infections were observed, and the quality of life in all three patients is excellent. During the SARS-CoV2 pandemic, all three patients were vaccinated with the mRNA vaccine, and they showed excellent humoral and cellular SARS-CoV2-specific immunity. Conclusions: Combined kidney and hematopoietic stem cell transplantation is a feasible and successful approach to induce specific immuno-logical tolerance in the setting of HLA-matched living kidney donation while maintaining immune responsiveness to a viral vaccine.