We report the long-term results from a reduced-intensity nonmyeloablative conditioning approach to establish high levels of donor chimerism without graft-versus-host disease (GVHD) in mismatched related and unrelated recipients of combined living donor kidney/hematopoietic facilitating cell/FCRx stem cell transplant. Recipients were conditioned with 200 cGy TBI plus fludarabine and cyclophosphamide and administered donor GCSF mobilized mononuclear cells, enriched for hematopoietic stem cells (HSC) and graft facilitating cells (FCs). Subjects ranged in age from 18 to 65 years. All subjects were HLA-disparate from their donors, ranging from 5 of 6 related to 0 of 6 unrelated. Eight were unrelated and 11 related. Subjects were maintained on tacrolimus and MMF for 6 months. At 6 months, if protocol biopsy is normal and chimerism present, the MMF is discontinued. The tacrolimus is discontinued at 12 months if stable renal function, normal protocol biopsy and chimerism are present. 30 subjects have been enrolled and 27 transplanted. Nineteen subjects have >1 year follow up. Twelve have achieved stable donor chimerism and have been successfully taken off immunosuppression. Time off IS ranges from 12 months to 54 months. We prospectively evaluated immune reconstitution and immunocompetence. Return of CD4⁺ and CD8⁺ T central and effector memory cell populations was rapid. TCR excision circle analysis indicated that >97% of chimeric cells are being produced de novo. The TCR repertoires post-transplant in chimeric subjects were distinct from donor or recipient pre-transplant. Of four subjects immunized for hepatitis B and whose donors were not, three retained immunologic memory after transplantation. Most chimeric subjects retained memory for measles, mumps, rubella and varicella. Chimeric subjects generated immune responses to pneumococcal vaccine. Opportunistic viral infections such as BK viremia and cytomegalovirus activation were absent after cessation of immunosuppression. These findings suggest that immunologic recovery is robust in chimeric subjects who receive kidney/FCRx.

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