OPTIMALIZATION OF IMMUNOSUPPRESSION AFTER PULMONARY TRANSPLANTATION

Abstract

742 Background: The successful use of tacrolimus (FK) and mycophenolic acid (MPA) after heart transplantation has persuaded us to assess this medication after lung transplantation. In this study, we compared three subsequent immunosuppressive protocols after single (SLTx) or bilateral(DLTx) lung transplantation using either cyclosporin (CyA) or FK in combination with azathioprine (aza) or MPA. Methods: A total of 80 lung transplantations were performed at our centre; 71 of these patients (pts) were included in this study. The first 34 pts were treated with CyA and aza (group I). Of the remaining 37 pts receiving FK (group II), 28 received FK and aza (group IIa), and 9 FK and MPA(group IIb). The dosage of all three drugs (CyA, FK and MPA) was adjusted according to trough levels. No meaningful differences were found in demographic or baseline characteristics. The mean recipient age was 41.9 and 41.3 years, the ratio of SLTx/DLTx 57.1/42.9% and 58.8/41.2% in groups I and II, respectively. All pts received additionally corticosteroids.Results: The discrepancy in mean observation periods (26.5 vs 14.7 months in groups I and II) led us to restrict the analysis of events to the first year post-transplantation only. The actuarial one-year survival rate was 70.6% for the CyA group and 94.3% for the FK group (p<0.02). Causes of death in the CyA group were sepsis (n=4), obliterative bronchiolitis(n=3), acute rejection (n=1), CMV infection (n=1), and pulmonary embolism(n=1), in the FK group liver failure (n=1), obliterative bronchiolitis (n=1), and sepsis (n=1). The number of acute rejection episodes (ARE) per patient was 1.5 for the CyA group versus 1.18 for the FK group (p<0.05). In the subgroup treated with FK and MPA (group IIb), only one mild acute rejection episode was observed (0.1 ARE/pt). The incidence of infection (CyA: 1.45 vs FK: 1.39 infections/patient) and their spectrum were comparable. The most frequently reported adverse events were diabetes mellitus (57% in the FK vs 23% the CyA group) and renal insufficiency (27% vs 15%) Conclusion: FK appears to be a more potent immunosuppressant after pulmonary transplantation when compared to CyA; the incidence of acute rejections is significantly reduced and the one year survival rate markedly improved. Since the frequency and severity of acute rejection episodes are the main risk factors for the development of obliterative bronchiolitis, further follow-up will be necessary to determine whether more potent immunosuppressive protocols, like the combination of tacrolimus and MPA, will also be able to reduce the incidence of chronic rejection.