Thorac Cardiovasc Surg 2004; 52
DOI: 10.1055/s-2004-816850

Sirolimus in combination with Tacrolimus for primary immunosuppression after lung (LTx) and heart-lung transplantation (HLTx)

J Groetzner 1, P Ueberfuhr 1, T Strauss 1, J Behr 1, I Bittmann 1, M Vogeser 1, I Kaczmarek 1, F Kur 1, P Lamm 1, B Meiser 1, R Hatz 1 B Reichart 1, and the Munich Lung Transplant Group
  • 1Dept. of Cardiac Surgery & The Munich Lung Transplant Group, LMU University Hospital Gro�hadern, Munich, Germany

Introduction: A prospective, controlled pilot trial was started to evaluate the efficacy of a Sirolimus (Sir)/Tacrolimus (Tac)-based immunosupressive regimen on acute and chronic rejection in de novo LTx/HLTx recipients.

Material and Methods: In this study 13 LTx and 2 HLTx-recipients (10 male, mean recipient age 45±9.8 years, mean donor age 37±11 years, mean ischemia-time 290±109min) received a Sir- and Tac-based immunosuppressive therapy. Both immunosuppressants were administered trough level adjusted (Sir: 4–8ng/ml; Tac: 5–10ng/ml), while steroid administration was minimized. Indications for Tx were fibrosis (n=7), COPD (n=2), cystic fibrosis (n=4), VSD with Eisenmenger's syndrome (n=2).

Results: After a mean follow up of 9±4 months, survival was 87%. Three acute rejection episodes (ARE) occurred overall (0.08ARE/100 pt.days). Mean tac/sir trough levels were 9.1±1.89 ng/ml and 5.3±1.78 ng/ml, respectively. The infection incidence was 1.8±1.4/patient. In 5 patients bronchial wound healing complications occurred: One patient developed severe bronchial airway dehiscence. Mean cholesterol-levels were 203±67mg/dl, mean creatinine-levels before transplantation 0.9±0.27mg/dl and at latest follow-up 1.17±0.51mg/dl.

Conclusions: Tac/Sir seems to be very efficacious in preventing AREs at low trough levels, while infection-incidence was comparable to alternative regimens. Severe bronchial wound healing complications occurred, possibly associated with Sir administration. Other adverse events were non-significant. Therefore, this combination seems to offer an option to decrease target trough levels of each drug minimizing the severity of long term side effects of each agent. Additionally, the possible impact of the antiproliferative effect of Sir on the incidence of obliterative bronchiolitis has to be awaited. Considering wound healing complications, onset of Sir application should be started after bronchial wound healing is complete.