Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: The induction of allograft tolerance through mixed lymphohematopoietic chimerism

Background Experimental and clinical evidence has demonstrated that the est ablishment of allogeneic chimerism after bone marrow transplantation may pr ovide donor-specific tolerance for solid organ allografts. Methods. Based on the preliminary results of a clinical trial using nonmyel oablative preparative therapy for the induction of mixed lymphohematopoieti c chimerism, we treated a 55-year-old woman with end stage renal disease se condary to multiple myeloma with a combined histocompatibility leukocyte an tigen-matched bone marrow and renal transplant after conditioning with cycl ophosphamide, antithymocyte globulin, and thymic irradiation. Results. The posttransplant course was notable for early normalization of r enal function, the absence of acute graft-versus-host disease, and the esta blishment of mixed lymphohematopoietic chimerism. Cyclosporine, which was t he only posttransplant immunosuppressive therapy, was tapered and discontin ued on day +73 posttransplant. No rejection episodes occurred, and renal fu nction remains normal on day +170 posttransplant (14 weeks after discontinu ing cyclosporine). Although there is presently no evidence of donor hematop oiesis, there is evidence of an ongoing antitumor response with a recent st aging evaluation showing no measurable urine kappa light chains. The patien t remains clinically well and is off all immunosuppressive therapy. Conclusion. This is the first report of the deliberate induction of mixed l ymphohematopoietic chimerism after a nonmyeloablative preparative regimen t o treat a hematological malignancy and to provide allotolerance for a solid organ transplant.