title: Antithymocyte globulin induction therapy adjusted for immunologic risk after heart transplantation.
abstract: BACKGROUND
  The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known.
  
  
  METHODS
  All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection.
  
  
  RESULTS
  Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS).
  
  
  CONCLUSIONS
  ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.
authors: Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California, USA. lawrence.czer@cshs.org
authors: L S C
authors: LS
authors: Czer
authors: A
authors: A
authors: Phan
authors: A
authors: A
authors: Ruzza
authors: M
authors: M
authors: Rafiei
authors: S
authors: S
authors: Setareh-Shenas
authors: M
authors: M
authors: Caceres
authors: M
authors: M
authors: Awad
authors: C
authors: C
authors: Soliman
authors: J
authors: J
authors: Mirocha
authors: M
authors: M
authors: De Robertis
authors: R M
authors: RM
authors: Kass
authors: A
authors: A
authors: Trento
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001706:Biopsy; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000208:ethnology / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents