title: Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy.
abstract: OBJECTIVE
  Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment.
  
  
  METHODS
  In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine).
  
  
  RESULTS
  Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience.
  
  
  CONCLUSIONS
  Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.
authors.affiliation: Department of Surgery, The University of Pittsburgh Medical Center, PA 15216, USA. mccurrykr@upmc.edu
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: McCurry
authors.forename: Aldo
authors.initials: A
authors.lastname: Iacono
authors.forename: Adrianna
authors.initials: A
authors.lastname: Zeevi
authors.forename: Samuel
authors.initials: S
authors.lastname: Yousem
authors.forename: Alin
authors.initials: A
authors.lastname: Girnita
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.forename: Diana
authors.initials: D
authors.lastname: Zaldonis
authors.forename: Bruce
authors.initials: B
authors.lastname: Johnson
authors.forename: Brack G
authors.initials: BG
authors.lastname: Hattler
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Starzl
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D011241:Prednisone; D016559:Tacrolimus