Tolerance Workshop Review

The First International Workshop for Clinical Tolerance sponsored by The Transplantation Society was held in Boston, Massachusetts, on March 14-15, 2014. Entitled “Tolerance - One Transplant for Life”, the meeting was conducted by an executive group, including Tatsuo Kawai, Joseph Leventhal, Joren C. Madsen, Samuel Strober, Laurence A. Turka, and Kathryn J. Wood.

This meeting was conceived to address the issue of how to make tolerance induction protocols a standard of care for appropriate transplant recipients. None of the attendees expected a solution to emerge during meeting, but rather all hoped to identify issues and barriers, and to begin to craft a path forward, and indeed by this metric the workshop was a success. The discussions explored several key points related to tolerance trials, including patient selection with the underlying cause of end-stage renal disease and pre-sensitization. There was agreement that certain forms of ESRD with a very high risk of recurrence, such as FSGS, as well as pre-existing DSA, should represent an exclusion to enrollment. Study design of tolerance trials was also an important focus. Control groups (possibly with randomization) treated with standard immunosuppressive protocols should address the question of whether trying to achieve tolerance leads to superior patient outcomes over the long-term compared with standard of care or drug minimization. Most discussants agreed that stable donor chimerism was sufficient to establish donor specific tolerance. Considerable time was spent debating how transient chimerism might establish a form of regulatory tolerance, and how that state might be identified and measured. There was also extensive discussion around the issue of making drug withdrawal as safe as possible. One over-arching conclusion of this discussion was the need to be more systematic and standardized in collecting and disseminating clinical and immune monitoring data. Finally, there was unanimous agreement that difficulties in securing funds for clinical trials was a major impediment to progress.