| Title: |
Induction of immune tolerance in living related human leukocyte antigen-matched kidney transplantation: A phase 3 randomized clinical trial. |
| Authors: |
Kaufman, Dixon B; Akkina, Sanjeev K; Stegall, Mark D; Piper, James B; Gaber, A Osama; Asch, William S; Busque, Stephan; Stites, Erik; De Vera, Michael; Srinivas, Titte R; Alonso, Diane; Shah, Ashesh, MD; Patel, Anup; Mai, Martin L; Chavin, Kenneth D; DebRoy, Meelie; Jittirat, Arksarapuk; Costa, Nadiesda; Cooper, Matthew; Vranic, Gayle; Laftavi, Mark R; Saidi, Reza F; Collette, Suzon; Brennan, Daniel C |
| Source: |
Department of Surgery |
| Publisher Information: |
LVHN Scholarly Works |
| Publication Year: |
2025 |
| Collection: |
Lehigh Valley Health Network: LVHN Scholarly Works |
| Subject Terms: |
Humans; Kidney Transplantation; Male; Adult; Female; Middle Aged; HLA Antigens; Graft Survival; Living Donors; Graft Rejection; Immune Tolerance; Follow-Up Studies; Transplantation Conditioning; Kidney Failure; Chronic; Prognosis; Kidney Function Tests; Immunosuppressive Agents; Department of Surgery; Medicine and Health Sciences |
| Description: |
This phase 3 multicenter, randomized, controlled clinical trial evaluated investigational cellular product (MDR-101) to produce immune tolerance vs standard of care, in kidney transplant recipients. Adult recipients of kidneys from 2-haplotype human leukocyte antigen-matched living siblings were randomized 2:1 to treatment (n = 20) or control (n = 10). The MDR-101 product was from the same kidney donor. Treatment recipients received a nonmyeloablative conditioning protocol with rabbit-antithymocyte globulin and low-dose total lymphoid irradiation (10 fractions). MDR-101 was infused (day 11). Steroids were withdrawn by day 10 and mycophenolate by day 39. Tacrolimus was continued until day 180 and tapered to withdrawal 1-year posttransplant if donor hematopoietic mixed chimerism was ≥5%. Controls received immunosuppression (IS) per institutional standard of care. Twenty recipients received the MDR-101 infusion, and none developed graft versus host disease. Nineteen (95%) successfully discontinued all IS approximately 1 year after kidney transplant. Fifteen (75%) reached the primary study endpoint of IS-free for >2 years. Four resumed IS: 1 with recurrent immunoglobulin A nephropathy; 1 with recurrent immunoglobulin A nephropathy and rejection; 1 with rejection; and 1 with borderline biopsy changes. Kidney transplant recipients receiving MDR-101 achieved donor mixed chimerism and functional immune tolerance for greater than 2 years with no death, graft loss, DSA, or graft versus host disease and demonstrated improved quality of life compared to standard treatment. |
| Document Type: |
text |
| Language: |
unknown |
| Relation: |
https://scholarlyworks.lvhn.org/surgery/8111; https://pubmed.ncbi.nlm.nih.gov/39922283/ |
| Availability: |
https://scholarlyworks.lvhn.org/surgery/8111; https://pubmed.ncbi.nlm.nih.gov/39922283/ |
| Accession Number: |
edsbas.78DE19C9 |
| Database: |
BASE |