• Thomas E Starzl, Noriko Murase, Kareem Abu-Elmagd, Edward A Gray, Ron Shapiro, Bijan Eghtesad, Robert J Corry, Mark L Jordan, Paulo Fontes, Tim Gayowski, Geoffrey Bond, Velma P Scantlebury, Santosh Potdar, Parmjeet Randhawa, Tong Wu, Adriana Zeevi, Michael A Nalesnik, Jennifer Woodward, Amadeo Marcos, Massimo Trucco, Anthony J Demetris, and John J Fung.
• Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. mangantl@msx.upmc.edu <mangantl@msx.upmc.edu>
• Lancet. 2003 May 3; 361 (9368): 150215101502-10.

BackgroundInsight 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.Methods82 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.FindingsWe 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).InterpretationThe 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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