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.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Transplantation |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
| Externally published | Yes |
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Keywords
- Alloantibody
- Clinical research/practice
- Crossmatch
- Heart transplantation/cardiology
- Pediatrics
- Sensitization
ASJC Scopus subject areas
- Immunology and Allergy
- Transplantation
- Pharmacology (medical)
Cite this
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. / Zuckerman, Warren A.; Zeevi, Adriana; Mason, Kristen L.; Feingold, Brian; Bentlejewski, Carol; Addonizio, Linda J.; Blume, Elizabeth D.; Canter, Charles E.; Dipchand, Anne I.; Hsu, Daphne T.; Shaddy, Robert E.; Mahle, William T.; Demetris, Anthony J.; Briscoe, David M.; Mohanakumar, Thalachallour; Ahearn, Joseph M.; Iklé, David N.; Armstrong, Brian D.; Morrison, Yvonne; Diop, Helena; Odim, Jonah; Webber, Steven A.
In: American Journal of Transplantation, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Study rationale, design, and pretransplantation alloantibody status
T2 - A first report of Clinical Trials in Organ Transplantation in Children-04 (CTOTC-04) in pediatric heart transplantation
AU - Zuckerman, Warren A.
AU - Zeevi, Adriana
AU - Mason, Kristen L.
AU - Feingold, Brian
AU - Bentlejewski, Carol
AU - Addonizio, Linda J.
AU - Blume, Elizabeth D.
AU - Canter, Charles E.
AU - Dipchand, Anne I.
AU - Hsu, Daphne T.
AU - Shaddy, Robert E.
AU - Mahle, William T.
AU - Demetris, Anthony J.
AU - Briscoe, David M.
AU - Mohanakumar, Thalachallour
AU - Ahearn, Joseph M.
AU - Iklé, David N.
AU - Armstrong, Brian D.
AU - Morrison, Yvonne
AU - Diop, Helena
AU - Odim, Jonah
AU - Webber, Steven A.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Alloantibody
KW - Clinical research/practice
KW - Crossmatch
KW - Heart transplantation/cardiology
KW - Pediatrics
KW - Sensitization
UR - http://www.scopus.com/inward/record.url?scp=85044252408&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044252408&partnerID=8YFLogxK
U2 - 10.1111/ajt.14695
DO - 10.1111/ajt.14695
M3 - Article
C2 - 29446208
AN - SCOPUS:85044252408
JO - American Journal of Transplantation
JF - American Journal of Transplantation
SN - 1600-6135
ER -