36 subjects have been 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 nonmyeloablative conditioning. Recipients received fludarabine (30mg/m2, days -5,-4,-3), cyclophosphamide (50mg/kg, day-3 and+3), 200 cGyTBI (day-1) followed by living donor KTx (day0). A G-CSF mobilized leukapheresis product was obtained from the donor pre-KTx, processed to remove graft-versus-host disease (GVHD)-producing cells yet retain CD34+ cells and FC, and cryopreserved until use day+1 post-KTx. 31 pts have reached > 1 yr of followup (range 17-89 mos) and are the focus of this analysis(remaining 5 pts are < 5 mos post Tx) . Pts ranged in age from 18-65 yrs. 13 pts had unrelated and 18 had related donors. MMF and tacrolimus based immunosuppression (IS) was weaned off at 1 yr if chimerism, normal renal fcn and normal KTx biopsy were noted. 30 of 31 pts exhibited peripheral blood donor chimerism at one month post KTx. Durable chimerism allowing for full IS withdrawal developed in 22 pts (time off IS from 4-79 mos); 18/22 of 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 pts off IS have shown no evidence of immune defect: they show robust T/B/ NK cell reconstitution and can be safely vaccinated and develop protective immunity. Transiently chimeric pts resumed endogenous hematopoiesis and were maintained on low-dose tacrolimus monotherapy. Late (> 4 yrs post-Tx) acute rejection was observed in two pts with transient chimerism who became noncompliant with IS. There have been two cases of GVHD. 1 pt exhibited grade 1-2 acute GI GVHD that was successfully treated with steroids; this pt has gone on to develop mild chronic GVHD. The 2nd subject presented late following development of symptoms with treatment resistant GI GVHD and associated CMV infection that proved fatal at 11 months post-Tx. A 2nd death occurred in a chimeric pt, a >100 pack yr smoker who developed lung cancer 4.5 years after KTx, >3 years off IS. Two additional graft losses occurred, both previously reported and related to infections. In summary, high levels of durable chimerism and tolerance with a low (6.4%) incidence of GVHD has been achieved in recipients of living donor KTx + FCRx.

CITATION INFORMATION: Leventhal J, Galvin J, Mathew J, Gallon L, Stare D, Sweeney A, Miller J, Abecassis M, Ildstad S. Eight Year Follow-Up of a Phase 2 Clinical Trial to Induce Tolerance in Living Donor Renal Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

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