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Am J Transplant. 2018 Sep;18(9):2135-2147. doi: 10.1111/ajt.14695. Epub 2018 Mar 23.

Study rationale, design, and pretransplantation alloantibody status: A first report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in pediatric heart transplantation.

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Division of Pediatric Cardiology, Columbia University Medical Center, New York, NY, USA.
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Rho Inc., Federal Systems Division, Chapel Hill, NC, USA.
Department of Pediatrics and Clinical and Translational Science, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pediatric Cardiology, Boston Children's Hospital, Boston, MA, USA.
Division of Pediatric Cardiology, Washington University School of Medicine, St. Louis, MO, USA.
Labatt Family Heart Center, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada.
Division of Pediatric Cardiology, Children's Hospital at Montefiore, Bronx, NY, USA.
Division of Pediatric Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Division of Pediatric Cardiology, Children's Healthcare of Atlanta, Atlanta, GA, USA.
Transplant Research Program, Division of Pediatric Nephrology, Harvard Medical School, Boston, MA, USA.
Norton Thoracic Institute, Saint Joseph Hospital and Medical Center, Phoenix, AZ, USA.
Department of Medicine, Allegheny Health Network, Pittsburgh, PA, USA.
Transplantation Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Division of Pediatric Cardiology, Monroe Carrell Jr. Children's Hospital at Vanderbilt, Nashville, TN, USA.


Anti-HLA donor-specific antibodies are associated with worse outcomes after organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase posttransplantation morbidity and mortality. We address this clinical challenge in a prospective, multicenter, observational cohort study of children listed for heart transplantation (Clinical Trials in Organ Transplantation in Children-04 [CTOTC-04]). Outcomes were compared among sensitized recipients who underwent transplantation with positive crossmatch, nonsensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC-04 report summarizes study rationale and design and relates pretransplantation sensitization status using solid-phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that more than half of patients were anti-HLA sensitized. Greater than 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one-third of sensitized patients had at least 1 HLA antibody with median fluorescence intensity of ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft, and ventricular assist device are independent risk factors for sensitization.


alloantibody; clinical research/practice; crossmatch; heart transplantation/cardiology; pediatrics; sensitization

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