Two Months Delayed Induction of Mixed Chimerism After Heart and Kidney Cotransplantation in Nonhuman Primates.
1Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA
2Department of Surgery, Massachusetts General Hospital, Boston, MA
3Department of Pathology, Massachusetts General Hospital, Boston, MA
4Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA
Meeting: 2017 American Transplant Congress
Abstract number: C272
Keywords: Bone marrow transplantation, Heart transplant patients, Tolerance
Session Information
Session Name: Poster Session C: Tolerance/Immune Regulation
Session Type: Poster Session
Date: Monday, May 1, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background We have previously achieved transplant tolerance in cynomolgus recipients cotransplanted with heart and kidney by treating recipients with standard triple drug immunosuppression for 4 months followed by mixed chimerism induction consisting of conditioning and bone marrow transplantation (BMT). Reducing the period of maintenance immunosuppression before BMT may diminish risks of immunosuppression-associated complications, post-transplant proliferative disorder (PTLD) and graft sensitization when applied to the clinic. Here we tested a more clinically relevant 2 month-delayed BMT protocol in heart plus kidney recipients.
Methods Following heart and kidney cotransplantation, recipients received tacrolimus, mycophenolate mofetil and methylprednisolone for 2 months after which they underwent nonmyeloablative conditioning and bone marrow transplantation (BMT). We divided recipients into 2 groups according to the conditioning regimens. Group A consisted of horse anti-thymocyte globulin, anti-CD154 mAb, and anti-CD8 mAb (n=3). Group B consisted of rabbit anti-thymocyte globulin and belatacept (n=4). Three Gy total body irradiation, 7 Gy local thymic irradiation, and 28 day course of cyclosporine were used in both groups. Allo-heart function was monitored by palpation, and serial protocol biopsies of allo-heart and kidney were performed to monitor graft rejection.
Results In group A, one recipient is currently day 531 post-BMT without rejection. However, two recipients were euthanized due to complications. In group B, two recipients are post BMT day 202 and 139 but show evidence of acute antibody-mediated rejection in allo-heart. Two other recipients were euthanized due to complications.
Conclusion Shortening the interval between organ and BM transplantation from 4 to 2 months permits tolerance induction. However, the efficacy and safety of including rabbit anti-thymoglobulin plus belatacept in the conditioning regimens requires further evaluation.
CITATION INFORMATION: Huh K, Sommer W, Robinson K, Wu X, Paster J, Hanekamp I, Dehnadi A, Kawai T, Smith R, Colvin R, Benichou G, Madsen J. Two Months Delayed Induction of Mixed Chimerism After Heart and Kidney Cotransplantation in Nonhuman Primates. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Huh K, Sommer W, Robinson K, Wu X, Paster J, Hanekamp I, Dehnadi A, Kawai T, Smith R, Colvin R, Benichou G, Madsen J. Two Months Delayed Induction of Mixed Chimerism After Heart and Kidney Cotransplantation in Nonhuman Primates. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/two-months-delayed-induction-of-mixed-chimerism-after-heart-and-kidney-cotransplantation-in-nonhuman-primates/. Accessed May 13, 2025.« Back to 2017 American Transplant Congress