title: ABO-incompatible heart transplantation in early childhood: an international multicenter study of clinical experiences and limits.
abstract: BACKGROUND
  Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries.
  
  
  METHODS
  Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey.
  
  
  RESULTS
  Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies.
  
  
  CONCLUSIONS
  Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. urschel@ualberta.ca
authors.forename: Simon
authors.initials: S
authors.lastname: Urschel
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Larsen
authors.forename: Richard
authors.initials: R
authors.lastname: Kirk
authors.forename: Julie
authors.initials: J
authors.lastname: Flett
authors.forename: Michael
authors.initials: M
authors.lastname: Burch
authors.forename: Nadine
authors.initials: N
authors.lastname: Shaw
authors.forename: Julia
authors.initials: J
authors.lastname: Birnbaum
authors.forename: Heinrich
authors.initials: H
authors.lastname: Netz
authors.forename: Elfriede
authors.initials: E
authors.lastname: Pahl
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Matthews
authors.forename: Richard
authors.initials: R
authors.lastname: Chinnock
authors.forename: Joyce K
authors.initials: JK
authors.lastname: Johnston
authors.forename: Kim
authors.initials: K
authors.lastname: Derkatz
authors.forename: Lori J
authors.initials: LJ
authors.lastname: West
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood / Q000276:immunology*; D001787:Blood Group Incompatibility / Q000097:blood / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies
chemical_list: D000017:ABO Blood-Group System