Presensitization: the problem and its management.

Much attention has been placed recently on transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful transplantation, several novel approaches have been developed. These include intravenous Ig (IVIg), mycophenolate mofetil, sirolimus, alemtuzumab, protein A immunoabsorption, and rituximab. IVIg has emerged as a very effective agent when used alone in high dose or when used in low dose and combined with plasmapheresis. Although alemtuzumab has been used to eliminated B cells, it fails to prevent antibody-mediated rejection and therefore probably is not suitable for desensitization. Rituximab, a B cell-specific antibody, seems to be safe and to have some efficacy as a sole agent in elimination of alloantibodies but most likely will require combination therapy with IVIg or other agents. Newer agents, such as humanized anti-CD20, are being developed. Despite the great interest in the problem of allosensitization, with one notable exception, there is a major deficiency in controlled clinical trials, the conduct of which should be a focus for the near future.