Delaying the Induction of Mixed Chimerism Until Two Months After NHP Heart and Kidney Cotransplantation Results in Long Term Survival.

K. Huh,¹ M. Tonsho,¹ P. Spencer,¹ J. Paster,¹ X. Wu,¹ I. Hanekamp,¹ T. Kawai,^1,3 R. Smith,² A. Cosimi,¹ A. Dehnadi,¹ G. Benichou,¹ R. Colvin,^1,2 J. Madsen.^1,4

¹Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA
²Department of Pathology, Massachusetts General Hospital, Boston, MA
³Department of Surgery, Massachusetts General Hospital, Boston, MA
⁴Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA.

Meeting: 2016 American Transplant Congress

Abstract number: D62

Keywords: Heart transplant patients, Mixed chimerism, Tolerance

Session Information

Session Name: Poster Session D: Chimerism/Stem Cells, Cellular/Islet Transplantation, Innate Immunity, Chronic Rejection

Session Type: Poster Session

Date: Tuesday, June 14, 2016

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Background. We have previously achieved delayed tolerance in cynomologous recipients cotransplanted with heart and kidney allografts by treating recipients with standard triple drug immunosuppression for 4 months followed by mixed chimerism conditioning and cryopreserved donor bone marrow transplantation (cBMT) then cessation of all drugs. Attempts to reduce the period of triple drug therapy from 4 months to 1 month were unsuccessful in recipients of isolated kidney allografts. Here we tested a 2 month-delayed cBMT protocol in heart plus kidney recipients.

Methods.Following heart and kidney cotransplantation, recipients received tacrolimus, mycophenolate mofetil and methylprednisolone for either 2 months (n=1) or 4 months (n=3) after which they underwent mixed chimerism conditioning (3 Gy total body irradiation, 7 Gy local thymic irradiation, anti-thymocyte globulin, anti-CD154 mAb, anti-CD8 mAb and a 28 day course of cyclosporine) and cBMT. Allo-heart function was monitored by palpation, and serial protocol biopsies of allo-heart and kidney were performed to monitor graft rejection.

Results. After cBMT, the same degree of transient mixed chimerism was observed in all 4 monkeys. Recipients in 4 month-delayed cBMT group survived >547, >588, >1093 days. The recipient in the 2 month-delayed cBMT is currently 222 days after transplantation with no evidence of rejection. Delayed tolerance in both groups was associated with donor-specific T cell hypo-/unresponsiveness and the absence of alloantibodies.

Conclusion. Delaying cBMT makes this mixed chimerism tolerance strategy applicable to recipients of cadaveric donors. Successfully reducing the period of maintenance immunosuppression before cBMT from 4 to 2 months should be associated with diminished risks of immunosuppression-associated complications, post-transplant proliferative disorder (PTLD) and graft sensitization when applied to the clinic.

CITATION INFORMATION: Huh K, Tonsho M, Spencer P, Paster J, Wu X, Hanekamp I, Kawai T, Smith R, Cosimi A, Dehnadi A, Benichou G, Colvin R, Madsen J. Delaying the Induction of Mixed Chimerism Until Two Months After NHP Heart and Kidney Cotransplantation Results in Long Term Survival. Am J Transplant. 2016;16 (suppl 3).

To cite this abstract in AMA style:

Huh K, Tonsho M, Spencer P, Paster J, Wu X, Hanekamp I, Kawai T, Smith R, Cosimi A, Dehnadi A, Benichou G, Colvin R, Madsen J. Delaying the Induction of Mixed Chimerism Until Two Months After NHP Heart and Kidney Cotransplantation Results in Long Term Survival. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/delaying-the-induction-of-mixed-chimerism-until-two-months-after-nhp-heart-and-kidney-cotransplantation-results-in-long-term-survival/. Accessed December 3, 2024.

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