title: Efficacy of tacrolimus in the treatment of refractory rejection in heart and lung transplant recipients.
abstract: BACKGROUND
  Refractory acute cellular rejection may occur despite triple-drug immunosuppression (cyclosporine A, steroids, azathioprine/mycophenolate mofetil). The purpose of this study was to determine the efficacy of tacrolimus rescue therapy in patients maintained on cyclosporine-based immunosuppression (CBI).
  
  
  METHODS
  Between December 1993 and October 1996, 208 patients underwent thoracic organ transplantation at the Hospital of the University of Wisconsin at Madison. One hundred forty-nine patients underwent heart replacement; 59 underwent lung transplantation. One hundred thirty-nine of the heart transplant cohort received CBI preceded by induction therapy with OKT3. Forty-six of the lung transplant cohort received CBI without induction cytolytic therapy. Refractory rejection was defined as failure to respond to high-dose steroids (500 mg to 1 g IV methylprednisolone for 3 days) and/or monoclonal antibody therapy (OKT3, 5 to 10 mg IV/day for 7 to 14 days). In patients with refractory rejection, cyclosporine was replaced with tacrolimus.
  
  
  RESULTS
  Overall, 16% (30/185) of patients receiving CBI experienced refractory rejection. Thirty-one episodes of grade IIIa or greater rejection occurred in 11% (15/139) of heart transplant recipients. Twenty episodes of grade II to IV rejection occurred in 33% (15/46) of lung transplant recipients. After tacrolimus rescue therapy, 93% (14/15) of patients in the heart transplant group converted to grade II or less rejection. Refractory rejection was reversed in 73% (11/15) of the lung transplant group. Reversal was documented at biopsy in all (8/8) lung recipients in whom it had been histologically identified. FEV1 values of 3 additional patients stabilized.
  
  
  CONCLUSIONS
  The incidence of refractory rejection in thoracic organ transplant recipients on CBI is significant. Reversal of refractory rejection follows rescue immunotherapy with tacrolimus.
authors.affiliation: Division of Cardiothoracic Surgery, University of Wisconsin School of Medicine, Madison, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Onsager
authors.forename: C C
authors.initials: CC
authors.lastname: Canver
authors.forename: M S
authors.initials: MS
authors.lastname: Jahania
authors.forename: D
authors.initials: D
authors.lastname: Welter
authors.forename: M
authors.initials: M
authors.lastname: Michalski
authors.forename: A M
authors.initials: AM
authors.lastname: Hoffman
authors.forename: R M
authors.initials: RM
authors.lastname: Mentzer
authors.forename: R B
authors.initials: RB
authors.lastname: Love
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001706:Biopsy; D016572:Cyclosporine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016041:Heart-Lung Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D016559:Tacrolimus