title: A prospective comparison of murine monoclonal CD-3 (OKT3) antibody-based and equine antithymocyte globulin-based rejection prophylaxis in cardiac transplantation. Decreased rejection and less corticosteroid use with OKT3.
abstract: To test the efficacy of murine monoclonal CD-3 antibody (OKT3) in early prophylaxis for cardiac allograft rejection, we conducted a 6-month trial, prospectively assigning 51 patients to receive either equine antithymocyte globulin-based (n = 25) or OKT3-based (n = 26) early prophylaxis. ATG patients received 8 days of ATG (10 mg/kg), with the first dose given preoperatively. OKT3 patients received 14 days of OKT3 (5 mg) beginning on the second postoperative day. Corticosteroid and azathioprine administration were similar during early prophylaxis. Cyclosporine was begun preoperatively in ATG patients and on the fourth postoperative day in OKT3 patients. In addition, patients in both groups were randomized to receive or not receive eight weekly administrations of vincristine (0.025 mg/kg). While infection rate (0.8 +/- 0.2 infections/patient in both groups [mean +/- SEM]) and mortality (1 patient in each group) did not differ, OKT3-based early prophylaxis delayed the first rejection episode (76 +/- 11 days vs. 36 +/- 8 days, P = 0.005) and decreased the risk of rejection during the 6-month follow-up (P less than 0.001, product-limit analysis). Overall, the OKT3 group manifested 1.5 +/- 0.2 episodes of rejection/patient compared with 2.2 +/- 0.2 episodes/patient in the ATG group (P = 0.036). Despite similar 6-month cumulative cyclosporine and azathioprine dosages, six month average corticosteroid administration was less in the OKT3 group (12.2 +/- 1.5 mg prednisone equivalent/m2/day versus 19.3 +/- 2.1 mg prednisone equivalent/m2/day, P = 0.008), fewer OKT3 patients subsequently required additional cytolytic therapy for rejection (2 [8%] versus 12 [48%], P = 0.001), and more patients in the OKT3 group were successfully weaned off maintenance corticosteroids (22 [88%] versus 11 [46%], P = 0.002). We conclude that, relative to an equine ATG-based protocol, OKT3-based early prophylaxis results in less rejection, permitting less chronic corticosteroid administration.
authors.affiliation: Division of Cardiology, University of Utah School of Medicine, Salt Lake City.
authors.forename: D G
authors.initials: DG
authors.lastname: Renlund
authors.forename: J B
authors.initials: JB
authors.lastname: O'Connell
authors.forename: E M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: M E
authors.initials: ME
authors.lastname: Hammond
authors.forename: N A
authors.initials: NA
authors.lastname: Burton
authors.forename: K W
authors.initials: KW
authors.lastname: Jones
authors.forename: S V
authors.initials: SV
authors.lastname: Karwande
authors.forename: D B
authors.initials: DB
authors.lastname: Doty
authors.forename: R L
authors.initials: RL
authors.lastname: Menlove
authors.forename: C M
authors.initials: CM
authors.lastname: Herrick
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D017252:CD3 Complex; D003524:Cyclosporins / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000961:Antilymphocyte Serum; D017252:CD3 Complex; D003524:Cyclosporins; D011948:Receptors, Antigen, T-Cell; D014750:Vincristine; D001379:Azathioprine