Tolerance and Withdrawal of Immunosuppressive Drugs in Patients Given Kidney and Hematopoietic Cell Transplants

Sixteen patients conditioned with total lymphoid irradiation and anti-thymocyte globulin were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA matched donors in a tolerance induction protocol. Blood cell monitoring included changes in chimerism, balance of T cell subsets, and responses to donor alloantigens. Fifteen patients developed multilineage chimerism without graft versus host disease (GVHD), and 8 with chimerism for at least 6 months were withdrawn from anti-rejection medications for 1 to 3 years (mean- 28 months) without subsequent rejection episodes. Four chimeric patients have just completed or are in the midst of drug withdrawal, and 4 patients were not withdrawn due to return of underlying disease or rejection episodes. Blood cells from all patients showed early high ratios of CD4+CD25+ regulatory T cells and NKT cells versus conventional naive CD4+ T cells, and those off drugs showed specific unresponsiveness to donor alloantigens. In conclusion, total lymphoid irradiation and anti-thymocyte globulin promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and hematopoietic donor cell infusions. All 16 patients had excellent graft function at the last observation point with or without maintenance drugs.