Health & Medical Organ Transplants & Donation

Alemtuzumab (Campath-1H) in Kidney Transplantation

Alemtuzumab (Campath-1H) in Kidney Transplantation
Kidney transplantation has become the treatment of choice for both the quality of life and survival in patients with end-stage renal disease (ESRD). However, the immunosuppressive regimen which allows optimal kidney transplant outcome remains elusive. One of the more promising induction agents, Alemtuzumab, was introduced to kidney transplantation by Calne in the late 1990s with low dose cyclosporine A monotherapy, with the hope of establishing ‘prope' or near tolerance. Subsequent pilot studies with Alemtuzumab alone or monotherapy (DSG, Rapa) demonstrated high rates of acute rejection (AR) along with occasional humoral components that lead to abandoning the concept of Alemtuzumab as a ‘magic bullet' to achieve tolerance, prope or otherwise. A number of programs (including our own) has since modified maintenance immunosuppression using low dose tacrolimus, and shown acceptable rates of AR, with relatively low incidence of viral infection and lymphoproliferative disorders along with cost benefit. However, there are only three prospective, randomized studies which are small with one year or less follow-up, and most published series utilize historical control groups with relatively short follow-up. As extrapolation from short-term data is far from secure, long-term, prospective, randomized studies with Alemtuzumab will be necessary to determine the optimal immunosuppressive regimen.

Progress in the development of immunosuppressive regimens has reduced the incidence and severity of acute rejection (AR) after renal transplantation. This has resulted in improved short-term (primarily 1 year) outcomes, but with less marked effects on long-term graft survival. This is due in part to the nephrotoxicity of calcineurin inhibitors (CNIs), the alloimmune component of transplant glomerulopathy, and other less well-defined processes. Regimens that can yield similar short-term results but with less long-term deterioration continue to be sought, perhaps even eventually allowing the development of immunologic tolerance.

New biologic agents such as (chimeric or humanized) monoclonal antibodies with longer half-lives have been introduced as induction therapy. The resulting prolonged biologic effect may allow lower dosages of (nephrotoxic) CNIs, both short- and long-term, and perhaps lower doses or avoidance of corticosteroids. One such agent is Alemtuzumab, a humanized CD52-specific complement fixing (cytotoxic-lymphodepleting) IgG1 monoclonal antibody first introduced in hemato-oncology by Waldmann and Hale, then in renal transplantation by Calne. The human CD52 antigen is found in variable concentrations on all peripheral blood mononuclear cells. Alemtuzumab profoundly depletes T cells from peripheral blood for several months with effects, albeit less marked, on B cells, natural killer cells, and monocytes, (in descending order) and with the least effect on CD34 (immature) hematopoetic stem cells. (see review 14).

Alemtuzumab is currently not indicated for organ transplantation and thus patients should be informed of its off-label use and its evolving experimental nature.

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