title: Mycophenolate mofetil versus azathioprine immunosuppressive regimens after lung transplantation: preliminary experience.
abstract: BACKGROUND
  Mycophenolate mofetil reduces episodes of biopsy-proven acute cellular rejection or treatment failure in the first year after kidney transplantation; however, limited data exist regarding the efficacy after lung transplantation.
  
  
  METHODS
  In a 2-center, nonrandomized concurrent cohort study (level III evidence), we analyzed the incidence of biopsy-proven acute cellular rejection (International Society for Heart and Lung Transplantation grade > or=A2) and decrement in pulmonary function during the first 12 months after successful lung transplantation. All patients received induction immunosuppression with antithymocyte globulin (< or=5 days' duration), cyclosporine and prednisone, in addition to either mycophenolate mofetil (2.0 g/d) [n=11] or azathioprine (1 to 2 mg/kg per day) [n=11].
  
  
  RESULTS
  During the first 12 months after lung transplantation, the mycophenolate mofetil group experienced significantly fewer episodes of acute cellular rejection than the azathioprine group (0.26+/-0.34 vs 0.72+/-0.43 episodes/100 patient-days [mean+/-SD], p < 0.01; 95% CI for the difference=0.126 to 0.813). The change in forced expiratory volume -1 second [deltaFEV1] (liters) between the 3rd and 12th months after lung transplantation was analyzed for the two treatment groups. For this interval, deltaFEV1 for the mycophenolate mofetil group was +0.158+/-0.497 L vs -0.281+/-0.406 L for the azathioprine group (p < 0.05; 95% CI for difference=+0.0356 to 0.843). During the first year, there was 1 death in each group attributed to bronchiolitis obliterans syndrome with concurrent pneumonia. There were no differences in incidence of cytomegalovirus or bacterial infections between the treatment groups; however, a higher prevalence of aspergillus sp airway colonization in bronchoalveolar lavage fluid was observed for the mycophenolate mofetil group (p < .05). The prevalence of bronchiolitis obliterans syndrome at 12 months was 36% for the azathioprine group vs 18% for the mycophenolate mofetil group (p=NS).
  
  
  CONCLUSIONS
  Our preliminary experience with mycophenolate mofetil after lung transplantation suggests a decreased incidence of biopsy-proven acute cellular rejection. Furthermore, less decline in FEV1 after 12 months may suggest a reduced incidence or delayed onset for development of bronchiolitis obliterans syndrome. Prospective randomized trials with low beta error (level I evidence) should be performed to assess the efficacy of mycophenolate mofetil vis-à-vis acute allograft rejection and bronchiolitis obliterans syndrome.
authors.affiliation: Cedars-Sinai Medical Center, Division of Pulmonary/Critical Care Medicine, Los Angeles, Calif 90048, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Ross
authors.forename: P F
authors.initials: PF
authors.lastname: Waters
authors.forename: M
authors.initials: M
authors.lastname: Levine
authors.forename: M
authors.initials: M
authors.lastname: Kramer
authors.forename: S
authors.initials: S
authors.lastname: Ruzevich
authors.forename: R M
authors.initials: RM
authors.lastname: Kass
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use*; D015331:Cohort Studies; D004311:Double-Blind Method; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D001379:Azathioprine