title: De-novo calcineurin-inhibitor-free immunosuppression with sirolimus and mycophenolate mofetil after heart transplantation: 5-year results.
abstract: OBJECTIVE
  Despite improvements in immunosuppressive therapy, chronic rejection, renal toxicity and malignancy are the major obstacles for long-term success after heart transplantation. We performed the worldwide first pilot-trial to evaluate the efficacy and safety of a de-novo calcineurin-inhibitor (CNI)-free immunosuppressive protocol. Between May 2003 and April 2005, 15 de-novo cardiac transplant recipients were assigned to receive sirolimus, mycophenolate mofetil and steroids. Antilymphocyte induction was given for 5 days; steroids were withdrawn after 6 months. A total of six of 15 patients received cytomegalovirus (CMV)-prophylaxis for high-risk CMV constellation (R-/D+).
  
  
  RESULTS
  Survival at 1 and 5 years was 87.5%. Freedom from biopsy-proven rejection was 71.3% at 1 year and 59.4% at 5 years. Freedom from angiographically detectable vasculopathy was 100% after 5 years and only one CMV infection occurred. Mean serum creatinine was 1.43 ± 0.31 mg/dl prior to heart transplantation (HTx), 1.29 ± 0.56 mg/dl at 1 year and 1.23 ± 0.53 mg/dl at 5 years. Cholesterol was 203 ± 32 mg/dl at 1 year and 199 ± 40 mg/dl at 5 years despite statins, and hypertriglyceridaemia (223 ± 97 mg/dl) persisted after 5 years. No new-onset diabetes occurred. Surgical interventions for pericardial effusions were necessary in five patients. Nine patients discontinued sirolimus treatment temporarily because of side-effects (four acute rejections, three delayed wound healing and two gastrointestinal toxicity), all nine patients were reintroduced to sirolimus after the side-effects resolved.
  
  
  CONCLUSIONS
  CNI-free immunosuppression is possible and long-term results are favourable for survival, malignancy, renal function, CMV infections and vasculopathy. On the other hand, de-novo CNI-free immunosuppression after HTx is less efficacious in preventing acute rejection and has an inferior side-effect profile.
authors.affiliation: Transplantation Center Munich, Munich, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Meiser
authors.forename: Stefan
authors.initials: S
authors.lastname: Buchholz
authors.forename: Ingo
authors.initials: I
authors.lastname: Kaczmarek
mesh_terms: D019703:Calcineurin / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006333:Heart Failure / Q000601:surgery*; D016027:Heart Transplantation / Q000379:methods*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011182:Postoperative Care / Q000379:methods; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D019703:Calcineurin; D009173:Mycophenolic Acid; D020123:Sirolimus