Management of rejection in heart transplant recipients: does moderate rejection always require treatment?

Triple-drug immunosuppression with cyclosporine, azathioprine, and steroids was introduced at Papworth Hospital in 1986. The management of rejection episodes in the first 40 patients receiving this regimen was reviewed for a minimal follow-up period of 18 months. Routine endomyocardial biopsy specimens were taken and classified into nil, minimal, mild, moderate, and severe rejection categories. Management was dependent on the biopsy result, in addition to the clinical state of the patient. In the early postoperative period (day 0 to 30) 2% of biopsy results showed severe rejection and 27% showed moderate rejection; all but one of the latter patients received augmentation of immunosuppression. In the intermediate period (days 31 to 90) severe rejection was present in 1% and moderate rejection in 36 (31%) of biopsies. Immunosuppression was augmented in 13 symptomatic patients, but in 23 asymptomatic patients additional therapy was withheld and the biopsy was repeated in 5 to 7 days. If moderate rejection was still present (11 cases), immunosuppression was augmented. Later (3 to 12 months) augmentation of immunosuppression was given on only four occasions. When the histologic criteria for diagnosis of moderate rejection are present during the early period after transplantation, we recommend augmented immunosuppression. In cases of later rejection we suggest that the decision be based on the biopsy result and the clinical condition of the patient; however, a prospective controlled trial will be required to confirm that this policy is correct.