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  • Title: Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression.
    Author: Laufer G, Miholic J, Laczkovics A, Wollenek G, Holzinger C, Hajek-Rosenmeier A, Wuzl G, Schreiner W, Buxbaum P, Wolner E.
    Journal: J Thorac Cardiovasc Surg; 1989 Dec; 98(6):1113-21. PubMed ID: 2586129.
    Abstract:
    To assess independent risk factors predicting the occurrence of clinically significant acute rejection episodes in the first 6 months after cardiac transplantation, we performed a multivariate stepwise logistic regression analysis. Forty-three recipients, undergoing transplantation between September 1986 and May 1988, were eligible for analysis and received standardized, low-dose triple drug maintenance immunosuppression with cyclosporine, azathioprine, and prednisolone. Immunoprophylaxis was supplemented perioperatively with either a polyclonal (antithymocyte globulin, N = 26) or a monoclonal (OKT3, N = 17) anti-T-cell antibody. Investigated, conceivable risk factors comprised recipient and donor age, ischemic time, perioperative anti-T-cell antibody prophylaxis, recipient preoperative status, underlying disease, previous cardiac operation, and histocompatibility parameter (mismatches for HLA-A, HLA-B, HLA-DR, HLA-B+DR, HLA-A+B+DR, and Rh0[D] antigen, HLA-DRw6 positive recipient, and identify for ABO system). Univariate analysis suggested significant influence of the type of antibody used perioperatively (p = 0.0024) and the number of mismatches for HLA-A+B+DR (p = 0.0037) and for HLA-B+DR (p = 0.0043). Stepwise logistic regression yielded the number of mismatches for HLA-B+DR (p = 0.0029) and the type of antibody used perioperatively (p = 0.0031) as being highly significant predictors of acute cardiac rejection. Six-month freedom from rejection was 100%, 41%, and 27% for recipients with two, three, and four mismatches for HLA-B+DR and 59% versus 22% for recipients with polyclonal versus monoclonal antibody prophylaxis. Similar to results with kidney transplantation, these results indicate that a poor donor/recipient match for combined HLA-B+DR loci constitutes an independent risk factor for acute graft rejection in low-dose triple drug immunosuppressed cardiac recipients, which stimulates the potential concept of prospective HLA matching. In our experience OKT3 prophylaxis provides significantly less effective prevention of acute rejection than a comparable course of antithymocyte globulin.
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