Date: Sunday, June 3, 2018
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall 4EF
Recurrence of the original cause of ESRD has been observed in trials of tolerance induction for kidney transplantation (KTx) where donor HSC have been used to effect immunomodulation. A common feature of these trials is the establishment of transient mixed chimerism in the majority of subjects. Since 2009 we have conducted a Phase 2 trial of combined HSC/living donor KTx in mismatched and unrelated pts where the stated goal has been the establishment of durable donor macrochimerism. We have hypothesized that durable chimerism will protect against native ESRD recurrence. Our protocol is based upon tolerogenic CD8+/TCR-facilitating cells (FCRx) and nonmyeloablative conditioning with fludarabine, cyclophosphamide, and 200 cGy TBI. 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. 36 subjects have reached at least 1 year of FU (range 12-105 months) and are the focus of this analysis. Subjects ranged in age from 18-65 years and were from 6/6 HLA matched related to 0/6 matched unrelated. 16 had unrelated and 20 had related donors. Two subjects were re-transplants. MMF and tacrolimus based immunosuppression (IS) was weaned and discontinued at 1 year if chimerism, normal renal fcn and normal KTx biopsy were noted. 12 pts in our trial had a cause of ESRD associated with disease recurrence post-TX ( 6 IgAN, 2 FSGS, 2 Membranous GN, 2 Alport's). 7/12 had durable chimerism established allowing full withdrawal of IS; none of these pts, including the two with FSGS, experienced disease recurrence. 3/12 pts had transient chimerism; one of these with Membranous GN developed disease recurrence which was successfully treated with rituximab. 2/12 pts failed to establish any donor chimerism; one of these with IgAN experienced disease recurrence successfully treated with corticosteroids. There were no graft losses or patient deaths in this patient subgroup. Renal function (eGFR) has been excellent (eGFR range 56-102 ml/min overall). In conclusion, the establishment of durable chimerism using our FCRx approach is associated with protection from recurrence of original ESRD. The FCRx approach may be particularly suited for patients at high risk for disease recurrence post-Tx, such as FSGS.
CITATION INFORMATION: Leventhal J., Gallon L., Mathew J., Miller J., Stare D., Ildstad S. Durable Donor Hematopoetic Stem Cell (HSC) Chimerism is Associated with Protection from Native Renal Disease Recurrence in Recipients of Combined HSC/Kidney Transplants Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Leventhal J, Gallon L, Mathew J, Miller J, Stare D, Ildstad S. Durable Donor Hematopoetic Stem Cell (HSC) Chimerism is Associated with Protection from Native Renal Disease Recurrence in Recipients of Combined HSC/Kidney Transplants [abstract]. https://atcmeetingabstracts.com/abstract/durable-donor-hematopoetic-stem-cell-hsc-chimerism-is-associated-with-protection-from-native-renal-disease-recurrence-in-recipients-of-combined-hsc-kidney-transplants/. Accessed October 31, 2020.
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