We recently reported that low-intensity conditioning combined with facilitating cell (FC)-enriched hematopoietic stem cell transplantation (FCRx) can safely achieve high level, durable donor chimerism in unrelated and related mismatched kidney transplant (KTx) recipients without GVHD. This is associated with stable renal function and successful withdrawal of immunosuppression (IS). We herein present interim follow-up of now 19 subjects and identification of a reliable biomarker for withdrawal of immunosuppression.
HLA-mismatched living donor KTx recipients received low-intensity conditioning (fludarabine, cyclophosphamide, 200 cGy TBI, days -4 to -1), KTx (day 0), and infusion of cryopreserved G-CSF mobilized FCRx (day +1). Multilineage chimerism was assessed prospectively by STR Analysis. Functional studies (MLR and CML) were performed to assess donor-specific hyporeactivity.
Subjects ranged in age from 18-65 years. 18 of 19 patients demonstrated peripheral blood macrochimerism at 1 month post-transplant, ranging from 6%-100%. The one patient who failed to engraft was highly sensitized (Class I PRA > 40%). No subjects developed acute/chronic GVHD or engraftment syndrome. Chimerism was transient in 4 patients. Durable multilineage (T, B, monocyte) chimerism was achieved in 13 patients. All patients demonstrated in vitro donor-specific hyporesponsiveness (DSH) by MLR +/- CML post-transplant regardless of chimerism status. However, DSH in patients who lost chimerism was not predictive of successful IS weaning, as 3 of 4 transiently chimeric patients with DSH had subclinical Banff 1A rejection on protocol biopsy. No chimeric subject has exhibited Banff 1A. 8 chimeric subjects are completely off IS from 1-27 months. The remainder are weaning.
The presence of durable, high level multilineage chimerism in combined kidney + FCRx recipients is a robust biomarker of tolerance. DSH alone in the first post-transplant year does not predict successful IS withdrawal or tolerance.
Tollerud, D.: Other, Regenerex, LLC, Officer. Bozulic, L.: Employee, Regenerex, LLC. King, B.: Employee, Regenerex, LLC. Ildstad, S.: Other, Regenerex, LLC, CEO.
To cite this abstract in AMA style:Leventhal J, Abecassis M, Miller J, Gallon L, Ravindra K, Tollerud D, Bozulic L, King B, Elliott M, Herzig G, Herzig R, Ildstad S. Chimerism and Tolerance without GVHD in Mismatched Recipients of Combined Hematopoietic Stem Cell/Kidney Transplants: Donor-Specific Hyporeactivity Is Not a Reliable Biomarker for Tolerance [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/chimerism-and-tolerance-without-gvhd-in-mismatched-recipients-of-combined-hematopoietic-stem-cellkidney-transplants-donor-specific-hyporeactivity-is-not-a-reliable-biomarker-for-tolerance/. Accessed August 9, 2020.
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