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Optimising Immunosuppression - A Look to the Future

This meeting report has concentrated mainly on how to optimise immunosuppression in transplantation using existing agents - particularly the new tormulation of cyclosporin A, Neoral The introduction of cyclosporin A in the early 1 980s transformed the tield ot transplantation and made it a viable life-saving intervention for fhoosands of people around the world. But it is now clear that the better ann more consistent absorption ot Neoral franslates into more accurate and predictahie immunosuppression with the subsequent ability to reduce acute rejection and, potentially, chronic rejection.

The evidence ot superior clinical outcomes in transplant patients maintained on Neoral which is emerging from clinical trials around the world is especially remarkable given that it now seems that monitoring ot Neoral therapy to date has been sub-optimal.

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"Acute and chronic rejection rates can only be subtanally reduced by the introduction of new therapies "

Several ot the key pres-entations at this meeting highlighted the need tor and the existence ot wore sensitive and accurate monitoring tools. If these new approaches to mon-itoring are adopted, they should reduce toxicity and relection rates still turther. However, optimising the use of Neoral alone cannot completely eradicate rejection and other torms of gratt failure. It is widely agreed that acute and chronic rejection rates can only be substantially reduced by the introduction and prudent concomitant use of new therapies (Figure 1).

One such therapy is fhe recenfly introduced mycophenolate mofefil which, as a replacement for azathioprine, has succeeded in reducing rejection rates during the first six months post transplant, although there are no short-or long-term benefits to graft survival. Another particularly exciting development in this field is the forthcoming introduction of the new IL-2 receptor monoclonal antibodies such as Simulec (basiliximab) and daclizumab. These have been designed to complement the action of Neoral. Clinical trials so tar suggest that these monoclonal antibodies significantly reduce the number of acute rejecfion episodes and are as safe as placebo. Another exciting class of new agenfs aimed at reducing rejection and gratt failure rates still further is the macrolide antibiotics, rapamycin, and the rapamycin analogue, RAD.

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While these developments in monitoring and drug therapy offer real hope for the future in terms of improving the long-term outcome for transplant recipients, their full benefits mill never be realised unless the supply of organ donors is increased. It is extremely frustrating for transplant surgeons that as immunosuppression continues to improve along with the outlook for transplant recipients, the waiting list for organs gets longer; the gap between supply and demand widens (Figure 2).

It is clear that the shortage of organs will never be overcome by increasing human donors and there is now a growing recognition that xenotransplantation, possibly through the development of transgenic pigs, is the most feasible future approach to increasing the number of organs available for transplantation. Given that surveys show that the public are generally in favour and tolerant of xenotransplantation and the ethical issues surrounding it, research into this area potentially holds the key to the future direction of transplantation.