36 subjects have been enrolled and 31 transplanted in a phase 2 protocol (IDE 13947) to induce tolerance in recipients of living donor renal allografts (KTx). The protocol is based upon tolerogenic CD8+/TCR-facilitating cells (FCRx) and 200 cGy TBI-based nonmyeloablative conditioning. Recipients received fludarabine (30mg/kg/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 peripheral blood mononuclear cell 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. Subjects ranged in age from 18-65 years and were from 6/6 HLA matched related to 0/6 matched unrelated. 12 subjects had unrelated and 19 had related donors. 30 of 31 subjects exhibited donor chimerism at one month post KTx. The one subject w.o chimerism (NW9) was highly sensitized (PRA>50%). MMF and tacrolimus based immunosuppression (IS) was weaned and discontinued at 1 year if chimerism, normal renal fcn and normal KTx biopsy were noted. There was a learning curve in the early phases of this study. Subjects NW1 and NW4 received a suboptimal cell dose and were only transiently chimeric (< 6 months). Another subject (NW11) with a high PRA (33%, maximum historic 64%) developed transient chimerism. Transiently chimeric subjects resumed endogenous hematopoiesis and are on low-dose IS with stable renal fcn. 1 subject (NW27) exhibited grade 1-2 GVHD that was successfully treated with corticosteroids. A second subject (NW33) developed concomitant Grade 2-3 GVHD and CMV disease and is undergoing treatment. There have been 2 KTx losses related to infections post-Tx. 1 and 5yr Pt survival is 100%. Durable chimerism allowing for full IS withdrawal developed in 19 subjects (time off IS ranging from 3 – 65 months). 16 subjects had “full” (> 98% donor) chimerism, and three subjects more mixed chimerism. All stable chimeric subjects retained chimerism after removal of IS and remain rejection-free, as demonstrated by protocol biopsy, while 3 of 5 who were transiently chimeric had subclinical rejection. In summary, high levels of durable chimerism and tolerance with low incidence of GVHD have been achieved in mismatched related/unrelated recipients of combined FCRx and living donor KTx .

CITATION INFORMATION: Leventhal J, Galvin J, Stare D, Gallon L, Miller J, Mathew J, Abecassis M, Ildstad S. Seven Year Follow-Up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Renal Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

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