THE IMPACT OF EARLY POSTOPERATIVE CYCLOSPORINE SERUM LEVELS ON THE INCIDENCE OF CARDIAC ALLOGRAFT-REJECTION

The introduction of cyclosporine A (CyA) into the immunosuppressive th erapy has significantly improved the results of heart transplantation (HTX). Its nephrotoxicity and hepatotoxicity, however, often limit the perioperative and postoperative use of this drug. The purpose of this retrospective study was to evaluate the effect of early postoperative CyA blood levels on the incidence of early as well as late cardiac re jection and patients' survival. Between October 1985 and June 1991, HT X was performed in 311 patients. Standard immunosuppression consisted of azathioprine (1-2 mg/kg), prednisolone (0.5 to 0.1 mg/kg) and CyA. Rabbit-antithymocyte-globulin (RATG - 1.5 mg/kg) was administered for the first 4 days postoperatively. Moderate rejection was treated with 3 x 500 mg methylprednisolone, severe rejection with RATG (1.5 mg/kg t hree times a day). Patients were excluded from this study because of a positive cross-matching, early death unrelated to rejection or altern ate forms of immunosuppression (n = 111). Follow-up was complete in 20 0 patients (mean age 44 +/- 11 ; 18 female, 182 male; 204 233 patient days) with a total of 5380 biopsies. The cohort was divided into group I (no CyA for day 0 to 2; n = 108) and group II (CyA during day 0 to 2; n = 92) according to the onset of CyA therapy. In 101 patients (gro up A) the mean CyA blood level was less than 150 ng/ml from day 0 to 1 4 and in 99 patients more than 150 ng/ml (group B). On the 60th (365th ) postoperative day the incidence of rejection per patient month for g roup I amounted to 0.84 (0.36) versus 0.93 (0.35) for group II, 0.84 ( 0.28) in group A and 0.93 (0.30) in group B with a survival of 94% (84 %) in group I, 96% (87%) in group II, 92% (84%) in group A and 97% (89 %) in group B. In conclusion, following HTX the onset of CyA therapy c an be postponed and the respective early CyA target trough levels decr eased (150 ng/ml) without disadvantages regarding the incidence of ear ly and late rejection or patient survival.