*Purpose: 37 subjects have been transplanted in a phase 2 protocol to induce tolerance in recipients of living donor renal allografts (KTx) based upon tolerogenic CD8⁺/TCR^–facilitating cells (FCRx) and nonmyeloablative conditioning.

*Methods: Recipients were conditioned with fludarabine (30mg/m2/dose, days -5,-4,-3), cyclophosphamide (50mg/kg/dose, day-3 and+3), 200 cGy TBI followed by KTx (day0). A G-CSF mobilized product was apheresed from the donor pre-KTx, processed to remove graft-versus-host disease (GVHD)-producing cells yet retain CD34⁺ cells and FC and infused day+1 post-KTx.

*Results: All subjects have reached at least 1 year of FU (range 23 – 117 months). Pts ranged in age from 18-65 years and were from 6/6 HLA matched related (n= 2) to 0/6 matched unrelated. 17 subjects had unrelated and 20 had related donors. Two subjects were re-transplants. MMF and tacrolimus immunosuppression (IS) was weaned and discontinued at 1 year if chimerism, normal renal fcn and normal KTx biopsy were noted. 35 of 37 subjects exhibited peripheral blood donor chimerism at one month. Durable chimerism allowing full IS withdrawal developed in 26 subjects (time off IS ranging from 12- 100 months); 23/26 of these pts showed >95% donor whole blood and T cell chimerism. All stable chimeric subjects retained chimerism after removal of IS and remain rejection-free. Long term chimeric subjects off IS have no evidence of immune defect: there have been no late opportunistic infections, they show robust T, B, and NK cell reconstitution, and they can be safely and effectively vaccinated and develop protective immunity. Transiently chimeric subjects resumed host-derived hematopoiesis and were maintained on low-dose IS with stable renal fcn. Late (> 4 yrs post-Tx) acute rejection occurred in two subjects with transient chimerism who became noncompliant. There have been two cases of GVHD. 1 subject exhibited grade 1-2 acute GI GVHD that responded to corticosteroids; this subject has gone on to develop mild chronic GVHD. The second subject presented late following development of symptoms and manifested treatment resistant GI GVHD with associated CMV that proved fatal at 11 months post-Tx. There have been two additional kidney graft losses, both previously reported and related to infections. A second subject death occurred in >100 pack year smoker who developed advanced stage lung cancer 4.5 years after KTx.

*Conclusions: Overall patient survival is 94.4% and death censored graft survival 94.1%. Tolerant FCRx subjects off IS had significantly better renal function than comparable KTx on SOC IS. Medical therapy for hypertension and hyperlipidemia was more common in SOC than tolerant pts. In summary, high levels of durable chimerism and tolerance with a low (5.5%) incidence of GVHD has been achieved in mismatched related/unrelated recipients of living donor KTx. We conclude there are significant long term medical benefits to establishing tolerance in KTx recipients using the FCRx approach.

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