The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy\nafter organ transplantation, has been considered the ââ?¬Å?Holy Grailââ?¬Â of transplantation. Experimentally, tolerance has been achieved\nthrough clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the\nestablishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance\nhas been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and\nkidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism.\nCombined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions\ncan be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an\nunderlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor\nhematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve\norgan transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been\nsuccessful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the\nachievement of specific tolerance may become more widely applicable.
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