Plasmapheresis and cyclophosphamide in the treatment of humoral rejection after heart transplantation

Background: Clinical reports on humoral rejection after heart transplantation showed that these episodes were often more severe than those mediated through T lymphocytes and that the patient's prognosis was significantly worsened. Methods: To evaluate the impact of plasmapheresis on the course of humoral rejection with hemodynamic compromise (HRHC) episodes, we retrospectively investigated the records of 1,108 heart transplant patients. All patients received triple-drug immunosuppression (cyclosporine a, azathioprine, prednisone) and cytolytic antibodies for induction. Between April 1986 and December 1990, HRHC episodes were treated with cortisone boli and cytolytic antibodies for at least 3 days (Group A). Between January 1991 and April 1999, HRHC episodes were treated with cortisone boli, cytolytic antibodies, and plasmapheresis for at least 3 days (Group B). All patients who survived their first HRHC episode received cyclophosphamide instead of azathioprine as maintenance immunosuppression. Results: Altogether we observed 29 HRHC episodes. In 11 cases, no therapy could be administered or the therapy regimen did not correspond to either Protocol A or B. In the remaining 18 HRHC episodes, 7 episodes in 7 patients were treated without plasmapheresis (Group A), but only 2 patients survived, whereas in 11 HRHC episodes in 6 patients, therapy included plasmapheresis (Group B) and all patients survived (p = 0.002). Four of 6 patients who received cyclophosphamide after their first HRHC episode experienced at least 1 further HRHC episode. Conclusions: Plasmapheresis seems to improve outcomes in HRHC. However, cyclophosphamide as a maintenance immunosuppressive drug failed to prevent further humoral rejection episodes.