Purpose: 37 pts have been transplanted since 2009 in a phase 2 protocol to induce tolerance in recipients of living donor renal allografts (KTx). The protocol is based upon tolerogenic CD8+/TCR-facilitating cells (FCR001) and nonmyeloablative conditioning.
Methods: Pts were conditioned with fludarabine (30mg/m2/dose, days -5,-4,-3), cyclophosphamide (50mg/kg/dose, day-3 and+3), 200 cGy TBI (day-1) followed by KTx (day0). A G-CSF mobilized  apheresis product was collected from the donor >2 weeks pre-KTx, processed to remove graft-versus-host disease (GVHD)-producing cells yet retain CD34+ cells and FC, and cryopreserved until administration on day+1 post-KTx. All pts have reached at least 3 years of FU (range 36 - 129 months) and are the focus of this analysis. Pts were ages 18-65 years. Donor-recipient HLA match ranged from  6/6 matched related to 0/6 matched unrelated; 17 were unrelated and 20 were related . Two pts were re-transplants. MMF + tacrolimus based immunosuppression (IS) was weaned and discontinued at 1 year post-KTx if chimerism, normal renal function and  biopsy were present. 
Results: 35 of 37 pts exhibited peripheral blood donor chimerism at one month post KTx. Durable chimerism, allowing for full IS withdrawal developed in 26 pts (time off IS 24- 112 months); the majority (23/26) of these pts showed full (>95%) donor whole blood and T cell chimerism. All stable chimeric pts retained chimerism after removal of IS and remain rejection-free. Long term chimeric pts off IS have shown no evidence of immune defects: they show robust lineage reconstitution, and can be safely/effectively vaccinated. Two pts off IS have had successful pregnancies. Transiently chimeric pts resumed endogenous hematopoiesis and were kept on low-dose IS with stable renal function. Late (> 4 yrs post-KTx) acute rejection occurred in two pts with transient chimerism who became noncompliant with IS. There have been two previously reported cases of GVHD; one treatment responsive, the other treatment resistant that contributed to a pt death. There have been two graft losses in our trial, both related to infections. Two additional pt deaths have occurred: one in a heavy (>100 pack year) smoker who developed advanced stage lung cancer 4.5 years after KTx, and the second in a chimeric pt 3.5 years after Tx who developed pneumococcal sepsis – notably, he did not comply with recommended vaccinations. Overall survival is 91.8% and death censored graft survival 94.1%. Tolerant FCR001 pts off IS have significantly better renal function than comparable KTx on standard of care (SOC) IS. Treatment for hypertension and hyperlipidemia is more common in SOC than tolerant FCR001 pts.
Conclusions: Durable chimerism and tolerance with a low incidence of GVHD (6% overall, 3% severe)  has been achieved in mismatched related/unrelated living donor Ktx. We conclude there are significant long-term medical benefits to establishing tolerance in KTx recipients using the FCR001 approach.