title: Pediatric heart transplantation in human leukocyte antigen sensitized patients: evolving management and assessment of intermediate-term outcomes in a high-risk population.
abstract: BACKGROUND
  There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens-sensitized pediatric HTx recipients.
  
  
  RESULTS
  We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; > 10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis +/- intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post-HTx. Seven had early acute cellular rejection (> or = ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients > 6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy.
  
  
  CONCLUSIONS
  Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell-directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes.
authors.affiliation: Department of Pediatrics, Division of Cardiology, The Hospital for Sick Children/University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stacey M
authors.initials: SM
authors.lastname: Pollock-BarZiv
authors.forename: Neal
authors.initials: N
authors.lastname: den Hollander
authors.forename: Bo-Yee
authors.initials: BY
authors.lastname: Ngan
authors.forename: Paul
authors.initials: P
authors.lastname: Kantor
authors.forename: Brian
authors.initials: B
authors.lastname: McCrindle
authors.forename: Lori J
authors.initials: LJ
authors.lastname: West
authors.forename: Anne I
authors.initials: AI
authors.lastname: Dipchand
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019468:Disease Management; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D006680:HLA Antigens / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology / Q000401:mortality*; D006801:Humans; D007114:Immunization; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens