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, Adriana Zeevi, Kristen L. Mason, Brian Feingold, Carol Bentlejewski, Linda J. Addonizio, Elizabeth D. Blume, Charles E. Canter, Anne I. Dipchand, Daphne T. Hsu, Robert E. Shaddy, William T. Mahle, Anthony J. Demetris, David M. Briscoe, Thalachallour Mohanakumar, Joseph M. Ahearn, David N. Iklé, Brian D. Armstrong, Yvonne Morrison, Helena DiopJonah Odim, Steven A. Webber

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 languageEnglish (US)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Isoantibodies
Organ Transplantation
Heart Transplantation
Clinical Trials
Pediatrics
Antibodies
Transplantation
Immunosuppression
Logistic Models
Tissue Donors
Heart-Assist Devices
Mortality
Observational Studies
Allografts
Heart Diseases
Adrenal Cortex Hormones
Cohort Studies
Fluorescence
Technology
Morbidity

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 journalArticle

Zuckerman, WA, Zeevi, A, Mason, KL, Feingold, B, Bentlejewski, C, Addonizio, LJ, Blume, ED, Canter, CE, Dipchand, AI, Hsu, DT, Shaddy, RE, Mahle, WT, Demetris, AJ, Briscoe, DM, Mohanakumar, T, Ahearn, JM, Iklé, DN, Armstrong, BD, Morrison, Y, Diop, H, Odim, J & Webber, SA 2018, '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', American Journal of Transplantation. https://doi.org/10.1111/ajt.14695
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. / 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. In: American Journal of Transplantation. 2018.
@article{b31be52df4f742b7a1b8bb47633f9c6b,
title = "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",
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",
author = "Zuckerman, {Warren A.} and Adriana Zeevi and Mason, {Kristen L.} and Brian Feingold and Carol Bentlejewski and Addonizio, {Linda J.} and Blume, {Elizabeth D.} and Canter, {Charles E.} and Dipchand, {Anne I.} and Hsu, {Daphne T.} and Shaddy, {Robert E.} and Mahle, {William T.} and Demetris, {Anthony J.} and Briscoe, {David M.} and Thalachallour Mohanakumar and Ahearn, {Joseph M.} and Ikl{\'e}, {David N.} and Armstrong, {Brian D.} and Yvonne Morrison and Helena Diop and Jonah Odim and Webber, {Steven A.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/ajt.14695",
language = "English (US)",
journal = "American Journal of Transplantation",
issn = "1600-6135",
publisher = "Wiley-Blackwell",

}

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 -