ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /

Please note that you are viewing an archived section from 2019 and some content may be unavailable. To unlock all content for 2019, please visit the archives.

Abstract: TH-PO1214

Durable Donor Hematopoietic Stem Cell (HSC) Chimerism Is Associated with Protection from Native Renal Autoimmune Disease Recurrence in Recipients of Combined Stem Cell/Kidney Transplants

Session Information

Category: Transplantation

  • No subcategory defined

Authors

  • Leventhal, Joseph Ross, Northwestern University, Chicago, Illinois, United States
  • Galvin, John Patrick, University of Illinois Chicago, Chicago, Illinois, United States
  • Gallon, Lorenzo G., Northwestern University, Chicago, Illinois, United States
  • Belshe, Dianne Stare, Northwestern University, Chicago, Illinois, United States
  • Tollerud, David, Talaris Therapeutics Inc., Louisville, Kentucky, United States
  • Ildstad, Suzanne T, Talaris Therapeutics Inc., Louisville, Kentucky, United States
Background

Recurrence of autoimmune disease (AD) that caused ESRD has been observed in standard of care (SOC) renal transplants (KTx). Since 2009 we have conducted a Phase 2 trial of combined stem cell/living donor kidney transplantation in mismatched related and unrelated subjects with the goal of establishing durable donor chimerism. Our phase 2 is now closed and we have analyzed disease-recurrence in durably chimeric vs. transiently chimeric subjects

Methods

We hypothesized that durable chimerism will protect against native AD recurrence. Our protocol is based on tolerogenic CD8+/TCR- facilitating cells (FC) and 200 cGy TBI-based nonmyeloablative conditioning with fludarabine (30mg/m2/dose, days -5,-4,-3), cyclophosphamide (50mg/kg/dose, day-3 and+3), 200 cGy TBI (day-1) followed by a living donor KTx (day0). A G-CSF mobilized apheresis product was collected from the donor >2 weeks pre-KTx, processed to remove graft-versus-host disease-producing cells yet retain HSC and FC (FCRx), and cryopreserved until infusion on day+1 post-KTx. 36 subjects are more than 1 year post-KTx (12-105 months). Subjects ranged in age from 18-65 years and were from 6/6 HLA matched related to 0/6 matched unrelated: 16 unrelated and 20 related donors. MMF and tacrolimus immunosuppression (IS) was weaned and discontinued at 1 year post-KTx if chimerism, normal renal function and normal KTx biopsy were noted.

Results

12 subjects had AD as the cause of ESRD (6 IgAN, 2 FSGS, 2 Membranous GN, 2 Alport’s). 7 had durable chimerism, allowing full withdrawal of IS; none had disease recurrence, including 2 with FSGS. 3 subjects had transient chimerism. In that cohort, Membranous GN recurred in 1 subject. 2 had no donor chimerism; 1 IgAN recurrence which resolved with corticosteroids. There were no graft losses or patient deaths in these 12 subjects. Renal function (eGFR) has been excellent (eGFR range 56-102 ml/min). In conclusion, durable chimerism using the FCR001 approach protects against recurrent AD.

Conclusion

The FCR001 approach may be particularly suited for patients at high risk for disease recurrence post-KTx, such as FSGS.

Funding

  • NIDDK Support