title: A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database: Incidence, therapies and outcomes.
abstract: Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT.
  
  
  
  We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed.
  
  
  
  An episode of AMR was identified in 179 of 1,596 (11%) HT recipients and in 246 of 705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%) and eculizumab (0.4%). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13%). Thirty-three patients (16%) died after developing AMR. Patient and graft survival were lower for the AMR+group. One- and 3-year survival after initial AMR diagnosis was 88% and 77%, respectively.
  
  
  
  In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.
authors.affiliation: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA. Electronic address: pthrush@luriechildrens.org.
authors.forename: Philip T
authors.initials: PT
authors.lastname: Thrush
authors.affiliation: Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
authors.forename: Elfriede
authors.initials: E
authors.lastname: Pahl
authors.affiliation: Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Naftel
authors.affiliation: Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pruitt
authors.affiliation: Department of Pediatric Cardiology, Children's Hospital Colorado, Aurora, Colorado, USA.
authors.forename: Melanie D
authors.initials: MD
authors.lastname: Everitt
authors.affiliation: Department of Pediatrics, Nationwide Children׳s Hospital, Columbus, Ohio, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Missler
authors.affiliation: Department of Cardiology, Phoenix Children's Hospital, Phoenix, Arizona, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Zangwill
authors.affiliation: Cardiorespiratory Division, Great Ormond Street Hospital for Children, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Burch
authors.affiliation: Department of Pediatrics, University of North Carolina Children's Hospital, Chapel Hill, North Carolina, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Hoffman
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Butts
authors.affiliation: Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Mahle
mesh_terms: D000906:Antibodies; D002648:Child; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D015994:Incidence; D016030:Kidney Transplantation; D012189:Retrospective Studies
chemical_list: D000906:Antibodies
keywords: acute cellular rejection; antibody-mediated rejection; heart transplantation; humoral rejection; immunotherapy; pediatrics; rejection