27 subjects have been transplanted in a phase 2 protocol (IDE 13947) based upon tolerogenic CD8⁺/TCR^– facilitating cells (FCRx) and 200 cGy TBI-based nonmyeloablative conditioning to induce tolerance in mismatched recipients of living donor renal allografts (KTx). Recipients were conditioned with fludarabine, cyclophosphamide, 200 cGy TBI (day-1) followed by a living donor KTx (day0). A G-CSF mobilized cell product was apheresed from the donor >2 weeks pre-KTx, processed to remove GVHD-producing cells yet retain CD34⁺ cells and FC, and cryopreserved until administration day+1. Subjects ranged in age from 18-65 years and were from 6/6 HLA matched related to 0/6 matched unrelated. 9 subjects had unrelated and 18 had related donors. 26 of 27 subjects exhibited engraftment. One subject without engraftment was highly sensitized (PRA>50%). MMF and tacrolimus based immunosuppression (IS) was weaned between 6 months and 1 year if chimerism, normal renal function and normal KTx biopsy were noted. There was a learning curve in the phase 1 portion of this study. Subjects #1 and #4 received a suboptimal cell dose and were only transiently chimeric (<6 months). Another subject with a high PRA (33%, maximum historic 64%) demonstrated only transient chimerism. Transiently chimeric subjects resumed endogenous hematopoiesis and are on low-dose tacrolimus monotherapy with stable renal function. 1 subject has exhibited steroid-responsive grade 1GVHD after early conversion from CNI due to CNI nephrotoxicity. Subject #2 (95% donor) developed viral sepsis at month 3 and thrombosed his KTx. He was successfully re-transplanted off study. Subject 19 developed recurrent infections of native polycystic kidneys that contributed to KTx loss at 9 months. The remaining subjects are either off all IS (n=12; 12 -54 months) or are tapering. No chimeric subject has developed rejection on protocol biopsy while 3 of 5 who were transiently chimeric had subclinical rejection. In summary, high levels of durable chimerism and tolerance with a low incidence (3.7%) of GVHD have been achieved in mismatched related/ unrelated recipients of living donor KTx.

« Back to 2015 American Transplant Congress