*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 (FCRx) 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 PBMC product was apheresed 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 day+1 post-KTx. All subjects have reached at least 3 years of FU (range 36 – 129 months) and are the focus of this analysis. Pts ranged in age from 18-65 yrs and were from 6/6 HLA matched related to 0/6 matched unrelated. 17 pts had unrelated and 20 had related donors. Two pts were re-transplants. MMF and tacrolimus based immunosuppression (IS) was weaned and d/c’d at 1 year if chimerism, normal renal fcn and normal KTx biopsy were noted.

*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 ranging from 24- 112 months); the majority (23/26) of these pts showed full (>95%) donor whole blood/T cell chimerism. All stable chimeric pts retained chimerism after removal of IS and remain rejection-free. Long term chimeric subjects off IS have shown no evidence of immune defect: they show robust lineage reconstitution, and they can be safely/effectively vaccinated. Transiently chimeric subjects resumed endogenous hematopoiesis and were maintained on low-dose IS with stable renal fcn. Late (> 4 yrs post-Tx) acute rejection occurred in two pts with transient chimerism who became noncompliant with IS. There have been two previously reported but no additional cases of GVHD. There have been three subject deaths; one in a pt with GVHD. one in a heavy (>100 pack year) smoker who developed advanced stage lung cancer 4.5 years after KTx, the third in a chimeric pt 3.5 years after KTx who developed pneumococcal sepsis – he was not compliant with recommended vaccinations. There have been two additional graft losses in our trial, both previously reported and related to infections. Overall pt survival is 91.8% and death censored graft survival 94.1%. Tolerant FCRx pts off IS have significantly better renal function than comparable KTx on SOC IS. Treatment for hypertension and hyperlipidemia is more common in SOC than tolerant FCRx pts

*Conclusions: 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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