CYCLOSPORINE A (CSA) VS. TACROLIMUS (TAC), IN COMBINATION WITH MYCOPHENOLATE MOFETIL (MMF) AND STEROIDS AS PRIMARY IMMUNOSUPPRESSION AFTER LUNG TRANSPLANTATION

Abstract

919 Background: CsA or Tac have been used mostly in combination with azathioprine (Aza) as primary immunosuppression after lung transplantation (LTX). Benefit or risk deriving from the combination of these drugs with MMF are yet unknown. Patients and Methods: In a prospective two-center open randomized trial, CsA+MMF+steroids were compared to Tac+MMF+steroids after primary LTX. All patients underwent induction therapy with rabbit-ATG over three days. The two groups were compared with regard to patient survival, freedom from acute allograft rejection (AAR), infectious episodes and side effects. Results: Between 9/97 and 9/98, 48 LTX recipients were randomized to receive either CsA (n=23) or Tac (n=25). Groups were comparable with regard to age, gender, transplant procedure, and CMV match. Mean follow-up was 185±104 and 241±115 days, respectively. Three- and 6-months survival was similar in the two groups (0.95 vs. 0.92, and 0.87 vs. 0.78, respectively; P=NS). Two patients from the CsA group were retransplanted, one for early graft failure on day 22 and one for ongoing rejection on day 50. Freedom from AAR at 3 and 6 months was comparable between groups (0.56 vs. 0.60 and 0.56 vs. 0.55, respectively; P=NS). Mean number of treated AAR episodes per 100 patient-days was higher in the CsA than in the Tac group, but the difference was not statistically significant (0.43±0.59 vs. 0.27±0.35, P=NS). Two patients from the CsA group required switch to Tac to control ongoing rejection, while no patient from the Tac group required switch to CsA. There was no difference in the incidence of bacterial or viral infections, but there was a trend towards more fungal infections in the Tac group (n=8 vs. n=1; P=NS), also accounting for two late deaths in this group. New onset diabetes mellitus was observed in the Tac group only (n=3). Conclusion: The combination Tac+MMF seems to own a slightly higher immunosuppressive potential as compared to CsA+MMF. In contrast to historical reports of CsA or Tac combined with Aza, the incidence of early rejections is favourably reduced for both drugs when combined with MMF. Caution should be paid to the elevated incidence of fungal infections with the combination Tac+MMF.