Progress in transplantation.

Transplantation is an important and, in most cases, the only available therapeutic option for saving the lives of patients with end-stage organ failure. Furthermore, transplantation is recognized as one of the major medical achievements over the last half century. Despite outstanding short-term graft and patient survival rates, organ transplantation continues to face several major challenges. These include a severe shortage of donor grafts, poor long-term graft survival resulting from chronic vascular rejection, and major side effects from long-term immunosuppressive therapy required for prevention of rejection. Over the next several years, it will be imperative to develop novel solutions to these challenges in organ transplantation. Increasing the availability and quality of organs for transplantation will reduce patient death while on the waiting list and facilitate long-term graft survival after transplantation. Further understanding of the molecular mechanisms of cell activation has led to the discovery of additional new immunosuppressive agents that can now be used to allow individualization of immunosuppressive therapy. There is also a need to develop new strategies to monitor the use of immunosuppressive agents to reduce the incidence and severity of renal and cardiovascular toxicity and the increased incidence of cancer in transplant patients. Inducing a state of transplantation tolerance (graft acceptance without requirement for long-term immunosuppression) further offers the hope of improving the longevity of transplanted organs and the quality of life resulting from avoidance of significant side effects associated with immunosuppressive therapy.