title: A prospective, randomized comparison of cyclophosphamide and azathioprine for early rejection prophylaxis after cardiac transplantation. Decreased sensitization to OKT3.
abstract: Humoral immune responses have been implicated in the pathogenesis of vascular rejection, allograft coronary artery disease, and sensitization to OKT3. Because cyclophosphamide (CP) is a potent suppressor of humoral immunity, we postulated that substituting cyclophosphamide for azathioprine (AZA) would be associated with a decrease in acute vascular rejection and sensitization to OKT3 in cardiac transplant recipients also receiving cyclosporine, corticosteroids, and perioperative OKT3. We prospectively randomized 119 patients to receive azathioprine (n = 61) or cyclophosphamide (n = 58) from the time of transplantation. Dosage was adjusted to target white blood cell (WBC) counts. At six weeks posttransplantation, cyclophosphamide was converted to azathioprine. Patients were followed for a mean of 321 +/- 16 days. At four weeks WBC (1000/mm3) was 9.2 +/- 0.4 (SEM) in the AZA group and 9.7 +/- 0.6 for the CP group (P = 0.4). No differences were noted between the CP and AZA groups in mean cellular grades of rejection (1.8 +/- 0.1 vs. 1.7 +/- 0.1), mean vascular grades of rejection (2.0 +/- 0.1 vs. 1.8 +/- 0.1), early treated rejection episodes (1.9 +/- 0.1 vs. 2.2 +/- 0.1) days to first treated cellular rejection (38 +/- 3 vs. 41 +/- 3), or the number of patients manifesting primarily vascular rejection (18 vs. 19). Major infections and survival did not differ between the two groups. Eight patients in the AZA group developed anti-OKT3 antibodies, whereas only one patient in the CP group did (P = 0.04). In the early posttransplant period cyclophosphamide decreases the incidence of sensitization to OKT3 and appears to be as effective as azathioprine in preventing both cellular and vascular rejection.
authors.affiliation: Department of Medicine, University of Utah Health Sciences Center, LDS Hospital 84132.
authors.forename: D O
authors.initials: DO
authors.lastname: Taylor
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
authors.forename: J B
authors.initials: JB
authors.lastname: O'Connell
authors.forename: R D
authors.initials: RD
authors.lastname: Ensley
authors.forename: S L
authors.initials: SL
authors.lastname: Olsen
authors.forename: E H
authors.initials: EH
authors.lastname: Hammond
authors.forename: L E
authors.initials: LE
authors.lastname: Wagoner
authors.forename: D G
authors.initials: DG
authors.lastname: Renlund
mesh_terms: D000917:Antibody Formation; D001379:Azathioprine / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007109:Immunity; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000276:immunology; D011292:Premedication; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D016853:Muromonab-CD3; D003520:Cyclophosphamide; D001379:Azathioprine