Transplantation 1994: the year in review.

Progress during 1994 has yielded important positive effects on the clinical practice of transplantation. During the span of one generation, organ transplantation has moved from an experimental endeavor to an established therapeutic modality. Technical advances have improved the safety of the surgical enterprise, such that the major focus of research is now immunosuppressive therapy. Although tacrolimus has been approved for use in liver transplantation, ongoing trials seek to establish its role in the immunosuppressive arsenal. Undoubtedly, the introduction of mycophenolate mofetil and Neoral in the coming year, and probably sirolimus shortly thereafter, will broaden the spectrum of immunosuppressive agents, thereby improving transplant results. The recently completed multicenter studies not only demonstrated effective cooperative efforts by the transplant community, but also offered new insights into the more efficient design of future clinical trials. Although rejection remains the major barrier to transplant success, increasingly it is recognized that improved outcomes demand a decreased spectrum of iatrogenic side effects that markedly increase morbidity. Thus, strides in immunosuppressive management must be evaluated both by mitigation of rejection episodes and by quality of life measures. The ultimate goal of achieving transplant tolerance is now being addressed in clinical studies. There is no universal agreement concerning the role of chimerism as a strategy for tolerance induction; preclinical studies suggest that refined donor-type antigens or selectively enriched donor-cell infusions represent more likely tolerogenic stimuli. The challenge of inducing immunologic tolerance remains an elusive goal as we approach the new millennium.