title: Induction therapy for pediatric and adult heart transplantation: comparison between OKT3 and daclizumab.
abstract: BACKGROUND
  Induction therapy can reduce morbidity and early mortality in pediatric and adult heart transplant recipients. Monoclonal and polyclonal agents are most widely used; they nonspecifically deplete the T-cell pool and are thus associated with drug-induced side effects. The cytokine release syndrome is one of the most problematic events associated with induction. Daclizumab, a highly humanized, specific interleukin-2 receptor blocker, may be efficacious to the monoclonal agent, OKT3. Due to its specific action and properties, the safety profile of this agent may be superior to OKT3.
  
  
  METHODS
  Forty subjects received daclizumab and their clinical outcomes were compared against a historical group of 40 subjects who received OKT3. Three- and six-month outcome measures included survival, rejection history, steroid burden, and complications.
  
  
  RESULTS
  Mortality was low between the groups with equivalent 6-month survival. No differences in rejection profile or time to the first significant rejection event were detected; no subject had severe acute rejection within the first 180 days. Steroid requirement for maintenance immunosuppression and treatment of rejection was also similar between the groups. Six-month prevalence for complications were significantly different; 55% of OKT3-treated subjects having at least one event compared to 33% of daclizumab-treated subjects (P=0.04). The likelihood of complications occurred within the first month after transplantation.
  
  
  CONCLUSIONS
  Daclizumab induction therapy is as efficacious as OKT3 in the prevention of early acute rejection after heart transplantation among pediatric and adult subjects. Complications related to the induction agent are significantly lower in the humanized product.
authors.affiliation: Division of Pediatric Cardiology, Stanford University, Palo Alto, CA 94304, USA. clifford@leland.stanford.edu
authors.forename: Clifford
authors.initials: C
authors.lastname: Chin
authors.forename: Sky
authors.initials: S
authors.lastname: Pittson
authors.forename: Helen
authors.initials: H
authors.lastname: Luikart
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: Robert
authors.initials: R
authors.lastname: Robbins
authors.forename: Bruce
authors.initials: B
authors.lastname: Reitz
authors.forename: Phillip
authors.initials: P
authors.lastname: Oyer
authors.forename: Hannah
authors.initials: H
authors.lastname: Valantine
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001706:Biopsy; D002648:Child; D000077561:Daclizumab; D004699:Endocardium / Q000473:pathology; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000627:therapeutic use*; D012189:Retrospective Studies; D012449:Safety; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D000077561:Daclizumab