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Observational Study
. 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

Warren A Zuckerman  1 , Adriana Zeevi  2 , Kristen L Mason  3 , Brian Feingold  4 , Carol Bentlejewski  2 , Linda J Addonizio  1 , Elizabeth D Blume  5 , Charles E Canter  6 , Anne I Dipchand  7 , Daphne T Hsu  8 , Robert E Shaddy  9 , William T Mahle  10 , Anthony J Demetris  2 , David M Briscoe  11 , Thalachallour Mohanakumar  12 , Joseph M Ahearn  13 , David N Iklé  3 , Brian D Armstrong  3 , Yvonne Morrison  14 , Helena Diop  14 , Jonah Odim  14 , Steven A Webber  15
Affiliations
Observational Study

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

Warren A Zuckerman et al. Am J Transplant. 2018 Sep.

Abstract

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.

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

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Conflict of interest statement

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1
Figure 1
CTOC-04 study design.
Figure 2
Figure 2
Consort diagram by core laboratory sensitization status (numbers based on actual enrollment).
See this image and copyright information in PMC

Comment in

References

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