title: Allosensitization and outcomes in pediatric heart transplantation.
abstract: BACKGROUND
  Allosensitization among children being considered for heart transplantation remains a great challenge. Controversy exists as to the best approach for those with elevated panel-reactive antibody (PRA) titers. We sought to define the association between elevated PRA and outcomes using data from the multi-institutional Pediatric Heart Transplant Study Group.
  
  
  METHODS
  Between January 1993 and December 2008, 3,016 patients (>1 month of age) were listed for heart transplantation. PRA data at listing were available for 2,500 (83%) patients, and 2,237 underwent transplantation with PRA data being available for 1,904 (85%). Because various PRA assays were employed (e.g., cell-based and solid phase) we entered the highest value regardless of methodology.
  
  
  RESULTS
  Among the factors associated with high PRA at transplant were Status 1 at listing, previous sternotomy and prior Norwood procedure. An elevated PRA at listing was associated with higher risk of death while waiting. Of subjects with PRA ≥ 50% only 57% were transplanted by 1 year on the waitlist, as compared with 76% of those with PRA <10%. Waitlist mortality for the highly allosensitized subjects (≥ PRA 50%) was 19% by 12 months. Survival at 1 year after transplantation was significantly lower in those with PRA ≥ 50% versus those with PRA <10% (73% vs 90%, respectively, p < 0.0001). Those with elevated PRA who had a negative prospective crossmatch had no difference in survival compared with those without allosensitization. There was no significant association between PRA levels and time to first rejection or development of coronary allograft vasculopathy.
  
  
  CONCLUSIONS
  Significant allosensitization is associated with more than a 2-fold increased risk of death within the first transplant year. Although prospective crossmatching abrogates the risk of post-transplant mortality, it may contribute to higher pre-transplant attrition due to longer waitlist times. There is a critical need for strategies to minimize the impact of allosensitization and antibody-mediated rejection immediately after transplantation.
authors.affiliation: Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia 30322, USA. wmahle@emory.edu
authors.forename: William T
authors.initials: WT
authors.lastname: Mahle
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tresler
authors.forename: R Erik
authors.initials: RE
authors.lastname: Edens
authors.forename: Paolo
authors.initials: P
authors.lastname: Rusconi
authors.forename: James F
authors.initials: JF
authors.lastname: George
authors.forename: David C
authors.initials: DC
authors.lastname: Naftel
authors.forename: Robert E
authors.initials: RE
authors.lastname: Shaddy
mesh_terms: D001788:Blood Grouping and Crossmatching / Q000379:methods*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006331:Heart Diseases / Q000601:surgery*; D016027:Heart Transplantation / Q000276:immunology* / Q000401:mortality; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies