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

https://doi.org/10.1016/S1053-2498(00)00211-4Get rights and content

Abstract

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.

Section snippets

Patients

Between April 1986 and April 1999, 1,108 orthotopic heart transplantations in 1,080 patients were performed. The mean age was 49.3 years (range, 1 week to 71 years), and 872 men and 208 women were transplantated. The indications were primary cardiomyopathy (61.8%), ischemic cardiomyopathy (30.7%), other secondary cardiomyopathies (3.5%), congenital heart disease (1.3%), and retransplantations (2.7%). All patients received triple-drug immunosuppression regimens with cyclosporine, azathioprine,

Results

We found no significant differences with regard to age, gender, indication for transplantation, or degree of sensitization (panel reactive antibodies) between Periods A and B, between neither the patients in general nor between the patients with rejection episodes with hemodynamic compromise (all p > 0.05).

Discussion

Comparing therapeutic blood purification during HRHC episodes (Group B) with a historical group of patients treated without plasmapheresis (Group A) limits the study. However, since the early 1990s we have obtained experimental evidence that blood purification is very effective in treating severe humoral rejection episodes.20, 21 Therefore, a prospective, randomized clinical trial seems unjustifiable. Furthermore, in both groups the patients received comparable induction and maintenance

Conclusion

Plasmapheresis, in addition to cytolytic antibodies, seems to improve outcomes in HRHC episodes after heart transplantation. Some patients showed “rejection disease” with myocardial impairment as well as rejection-related SIRS. In these episodes, plasmapheresis not only led to immediate myocardial recovery but also to restitution of peripheral resistance. However, in our patients, cyclophosphamide, as a maintenance immunosuppressive drug, failed to prevent further severe humoral rejection

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