title: Independent risk factors predicting acute graft rejection in cardiac transplant recipients treated by triple drug immunosuppression.
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.
authors.affiliation: Department of Surgery II, University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Laufer
authors.forename: J
authors.initials: J
authors.lastname: Miholic
authors.forename: A
authors.initials: A
authors.lastname: Laczkovics
authors.forename: G
authors.initials: G
authors.lastname: Wollenek
authors.forename: C
authors.initials: C
authors.lastname: Holzinger
authors.forename: A
authors.initials: A
authors.lastname: Hajek-Rosenmeier
authors.forename: G
authors.initials: G
authors.lastname: Wuzl
authors.forename: W
authors.initials: W
authors.lastname: Schreiner
authors.forename: P
authors.initials: P
authors.lastname: Buxbaum
authors.forename: E
authors.initials: E
authors.lastname: Wolner
mesh_terms: D000208:Acute Disease; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001379:Azathioprine / Q000008:administration & dosage; D003524:Cyclosporins / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000032:analysis; D016027:Heart Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011239:Prednisolone / Q000008:administration & dosage; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D003524:Cyclosporins; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011239:Prednisolone; D001379:Azathioprine