Study of Combined Kidney and Blood Stem Cell Transplant From a Brother or Sister Donor

In spite of the pronounced benefit of kidney transplantation in prolonging survival and improving the quality of life of patients with end stage renal disease, it is still hampered by the risk of graft rejection and the need for lifelong immunosuppression. Researchers have sought to circumvent these challenges through the use of combined kidney and hematopoietic stem cell transplantation to induce immune tolerance. This study will build upon published reports showing favorable results for the TLI/rATG regimen in HLA-matched living donor transplant recipients. The investigators seek to confirm that patients treated with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG) followed by human leukocyte antigen (HLA)-identical donor hematopoietic progenitor cell transplant can be withdrawn from immunosuppressive drugs while maintaining normal renal function after renal transplantation. At serial time points, (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, and (3) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue tacrolimus at 12 months if the following conditions are met: (1) chimerism (defined as ≥5% donor type cells among the T cells, B cells, Natural Killer \[NK\] cells, and granulocytes) is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) stable graft function without clinical rejection episodes is maintained, (3) there is lack of histologic rejection on protocol biopsies, and (4) there is no evidence of graft vs. host disease (GVHD). Recipients in the proposed study will be given a target dose of ≥ 5 x106 CD34+ cells/kg and 5x106 CD3+ cells/kg with the goal of achieving durable mixed chimerism.