Cardiac transplantation, acute allograft rejection

Cardiac/Hepatic allograft rejection Treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant patients. 

Muromonab-(CD3) Orthoclone OKT3) is a mouse monoclonal antibody that is a purified IgG. It is used for the prevention of acute allograft rejection in kidney and hepatic transplants and as prophylaxis in cardiac transplantation. It is also used to deplete T cells in marrow from donors before bone marrow transplantation. 

B. Indications and use Orthoclone OKT3 is indicated for the treatment of acute allograft rejection in renal transplant patients and for the treatment of steroid-resistant acute allograft rejection in cardiac and hepatic transplant patients. 

Muromonoab-CD3 is used for the treatment of acute organ transplant rejection. It is effective in preventing graft rejection after kidney, heart or liver transplantation. Muromonoab-CD3 is effective in patients who after acute cardiac or liver allograft rejection do not respond to steroid therapy. It is administered intravenously and with a dose of 5 mg/day, a general concentration range of 400-1500 ng/ml can be achieved. A serum concentration of 600-1150 ng/ml in renal transplant patients produces desirable immunosuppressive effects. The levels of CD3 expression, their production and antibodies to the drug determine its rate of clearance. In the absence of antibodies to muromonoab-CD3, its half-life is about 18 h. 

Bishop DK, Shelby J, Eichwald EJ. 1992. Mobilization of T lymphocytes following cardiac transplantation. Evidence that CD4- positive cells are required for cytotoxic T lymphocyte activation, inflammatory endothelial development, graft infiltration and acute allograft rejection. Transplantation. 53 849-857. 

Poston RS, Mann MJ, Hoyt EG, Ennen M, Dzau VJ, Robbins RC. Antisense oligodeoxynucleotides prevent acute cardiac allograft rejection via a novel, non-toxic, highly efficient transfection method. Transplantation 1999 68 825-832. 

Pally, C. et al. (2008) The chemokine receptor Cxcr3 is not essential for acute cardiac allograft rejection in mice and rats. American Journal of Transplantation, 8, 1604-1613. 

Bowdish, M.F., Barr, M.L., Quardt, S.M., Medina, J., Collins, T., Johnson, M., Tonn, G., Newland, D. et al. (2003) Fvaluation of an oral CXCR3 antagonist in a rat model of acute cardiac allograft rejection. The Journal of Heart and Lung Transplantation, 22, S162. 

Barnard CN (1968) Human cardiac transplantation an evaluation of the first two operations performed at the Groote Schuur Hospital, Cape Town. Am J Cardiol 22 791-803 Batista RJV, Santos JLV, Takeshita N et al (1996) Partial left ventriculectomy to improve left ventricular function in end-stage heart disease. J Cardiac Surg 11 96-97 Billingham ME (1985) Endomyocardial biopsy detection of acute rejection in cardiac allograft recipients. Heart Vessels Suppl 1 86-90... 

Cyclosporine, proprietary names Sandimmune (cyclosporine) and Neoral, is a cyclic peptide composed of 11 amino acids, some of novel structure, isolated from the fungus Trichoderma polysporum (Figure 33-13). The compound has been shown effective in suppressing acute rejection in recipients of allograft organ transplants. Cyclosporine is approved for use in renal, cardiac, hepatic, pancreatic, and bone marrow transplants. 

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