Tolerogenic immunosuppression for organ transplantation

Starzl, TE and Murase, N and Abu-Elmagd, K and Gray, EA and Shapiro, R and Eghtesad, B and Corry, RJ and Jordan, ML and Fontes, P and Gayowski, T and Bond, G and Scantlebury, VP and Potdar, S and Randhawa, P and Wu, T and Zeevi, A and Nalesnik, MA and Woodward, J and Marcos, A and Trucco, M and Demetris, AJ and Fung, JJ (2003) Tolerogenic immunosuppression for organ transplantation. Lancet, 361 (9368). 1502 - 1510. ISSN 0140-6736

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Abstract

Background: Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants. Methods: 82 patients awaiting kidney, liver, pancreas, or intestinal transplantation were pretreated with about 5 mg/kg of a broadly reacting rabbit antithymocyte globulin during several hours. Post-transplant immunosuppression was restricted to tacrolimus unless additional drugs were needed to treat breakthrough rejection. After 4 months, patients on tacrolimus monotherapy were considered for dose-spacing to every other day or longer intervals. Findings: We frequently saw evidence of immune activation in graft biopsy samples, but unless this was associated with graft dysfunction or serious immune destruction, treatment usually was not intensified. Immunosuppression-related morbidity was virtually eliminated. 78 (95%) of 82 patients survived at 1 year and at 13-18 months. Graft survival was 73 (89%) of 82 at 1 year and 72 (88%) of 82 at 13-18 months. Of the 72 recipients with surviving grafts, 43 are on spaced doses of tacrolimus monotherapy: every other day (n=6), three times per week (11), twice per week (15), or once per week (11). Interpretation: The striking ability to wean immunosuppression in these recipients indicates variable induction of tolerance. The simple therapeutic principles are neither drug-specific nor organ-specific. Systematic application of these principles should allow improvements in quality of life and long-term survival after organ transplantation.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Starzl, TE tes11@pitt.edu TES11 Murase, N Abu-Elmagd, K Gray, EA Shapiro, R Eghtesad, B Corry, RJ Jordan, ML Fontes, P Gayowski, T Bond, G Scantlebury, VP Potdar, S Randhawa, P Wu, T Zeevi, A Nalesnik, MA nalesnik@pitt.edu NALESNIK Woodward, J jew7@pitt.edu JEW7 Marcos, A Trucco, M mnt@pitt.edu MNT Demetris, AJ Fung, JJ
Centers:	Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date:	3 May 2003
Date Type:	Publication
Journal or Publication Title:	Lancet
Volume:	361
Number:	9368
Page Range:	1502 - 1510
DOI or Unique Handle:	10.1016/s0140-6736(03)13175-3
Institution:	University of Pittsburgh
Refereed:	Yes
ISSN:	0140-6736
Other ID:	uls-drl:31735062120963, Starzl CV No. 2184
Date Deposited:	08 Apr 2010 17:37
Last Modified:	02 Feb 2019 16:58
URI:	http://d-scholarship.pitt.edu/id/eprint/5570

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