A prospective, randomized comparison of cyclophosphamide and azathioprine for early rejection prophylaxis after cardiac transplantation. Decreased sensitization to OKT3.
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.
Taylor
D O
DO
Department of Medicine, University of Utah Health Sciences Center, LDS Hospital 84132.
Bristow
M R
MR
O'Connell
J B
JB
Ensley
R D
RD
Olsen
S L
SL
Hammond
E H
EH
Wagoner
L E
LE
Renlund
D G
DG
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
D016853:Muromonab-CD3; D003520:Cyclophosphamide; D001379:Azathioprine