title: Late acute cardiac allograft rejection: new therapeutic options?
abstract: BACKGROUND
  Late acute cellular rejection is associated with decreased survival and the development of CAV. Among new immunosuppressive drugs introduced into clinical practice, everolimus, has been shown to be safe in cardiac transplantation. We report our experience with everolimus in heart transplant recipients who developed late acute cellular cardiac rejection.
  
  
  METHODS
  Patients with a history of previous rejection episodes who experienced cardiac rejection were switched to an everolimus, cyclosporine, and steroid immunosuppressive regimen. All patients had already received statins and antihypertensive medications. Everolimus, cyclosporine trough levels, and laboratory values were controlled monthly. Drug administration was adapted to an everolimus trough level between 3 and 8 ng/mL, mean maintenance dosage was 0.25 to 1.5 mg twice a day. Death, safety, side effects, biopsy-proven acute rejection episodes, laboratory values, and blood levels were evaluated retrospectively.
  
  
  RESULTS
  Four cardiac allograft recipients (two male, two female), at a median of 1473.25 days post-orthotopic heart transplantation (oHTx) (range = 65 to 3045), received 1 to 1.5 mg everolimus per day. Over a follow-up period of at least 2 month (range = 2 to 10) the mortality was 0%. The drug was well tolerated; no acute cellular rejection greater than grade 1a (ISHLT grading) was observed after 2 months. In one patient increased cholesterol values and in two others, elevated triglyceride levels were seen, but were controlled with increased statin therapy. No obvious increased creatinine values were seen with everolimus.
  
  
  CONCLUSIONS
  In conclusion, conversion to an everolimus-based immunosuppressive regimen after late cardiac rejection is safe and effective; no major side effects were observed.
authors.affiliation: Department for Transplantation, Medical University Graz, University of Surgery, Graz, Austria. martin.schweiger@klinikum-graz.at
authors.forename: M
authors.initials: M
authors.lastname: Schweiger
authors.forename: A
authors.initials: A
authors.lastname: Wasler
authors.forename: G
authors.initials: G
authors.lastname: Prenner
authors.forename: M
authors.initials: M
authors.lastname: Tripolt
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.forename: K H
authors.initials: KH
authors.lastname: Tscheliessnigg
mesh_terms: D000208:Acute Disease; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D020123:Sirolimus