Transplantation tolerance: from theory to clinic

Tolerance induction and alloreactivity can be applied to the clinic for the transplantation of solid organs and in the treatment of human cancers respectively. Hematopoietic chimerism, the stable coexistence of host and donor blood cells, guarantees that a solid organ from the same donor will be tolerated without a requirement for maintenance immunosuppression, and it also serves as a platform for the adoptive immunotherapy of hematologic malignancies using donor lymphocyte infusions. This review focuses on clinically relevant methods for inducing hematopoietic chimerism and transplantation tolerance, with a special emphasis on reduced intensity transplantation conditioning and high dose, post-transplantation cyclophosphamide to prevent graft rejection and graft-versus-host disease (GVHD). Reduced intensity transplantation regimens permit a transient cooperation between donor and host immune systems to eradicate malignancy without producing GVHD. Their favorable toxicity profile also enables the application of allogeneic stem cell transplantation to treat non-malignant disorders of hematopoiesis and to induce tolerance for solid organ transplantation.