IMPROVED IMMUNOSUPPRESSION FOR HEART TRANSPLANT PATIENTS USING INTRAVENOUS DOSES OF CYCLOSPORINE

Abstract

Inducing immunosuppression in heart transplant patients with intravenous doses of CsA may decrease the incidence of severe rejection in the 1st month after operation. In our initial series, 16 consecutive patients (group A) who had no contraindications to this type of therapy received an i.v. dose of CsA, 1 mg/kg/day, postoperatively, which was then increased by 1 mg/kg every 24 hr until a full maintenance dose of 4 mg/kg/day was achieved (total time, 72 hr). The gradual increase in dosage was designed to prevent nephrotoxicity associated with higher doses of CsA. Intravenous administration was continued for 2 weeks, at which time oral administration of CsA, 14 mg/kg/day, was begun. In a subsequent series, 21 similar patients (group B) received the same amount of CsA, except that doses were increased every 12 hr, so that the full maintenance dose was achieved 36 hr postoperatively. In group B, the i.v. dose of CsA was continued for only 1 week, at which time oral administration of CsA, 14 mg/kg/day, was begun. All patients received the same standard steroid taper (30 mg/day by day 10). Patients from both groups who were greater than or equal to 55 years old and had serum creatinine greater than or equal to 1.5 mg/dl and patients from group B who had creatinine clearance less than or equal to 55 ml/min also received azathioprine, 2 mg/day, which was adjusted to maintain the white blood cell count at a level greater than or equal to 5000/cc. There was a similar number of such patients in both groups. Severe rejection was defined by endomyocardial biopsy with frequent foci of myocyte degeneration. Three (18.7%) patients in group A experienced severe rejection, and 2 (9.4%) in group B did. No patients developed renal failure. All patients survived the 1st month. The overall survival rate for group A at 12.2 +/- 1.5 months was 94%, and for group B it was 86% at 7.5 +/- 1.4 months. Both these groups compared favorably with our historical control group of patients who received oral doses of CsA to induce immunosuppression, in which 59 of 165 (35.8%) had severe rejection in the 1st month, with a 1-year actuarial survival rate of 76%. Based on this experience, we believe that i.v. administration of CsA enhances the induction of immunosuppression, thereby reducing the incidence of severe rejection. This protocol is likely to be effective because it minimizes the problems of oral absorption in the perioperative period.(ABSTRACT TRUNCATED AT 400 WORDS)