A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database: Incidence, therapies and outcomes

Philip T. Thrush, Elfriede Pahl, David C. Naftel, Elizabeth Pruitt, Melanie D. Everitt, Heather Missler, Steven Zangwill, Michael Burch, Timothy M. Hoffman, Ryan Butts, William T. Mahle

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Abstract

Background Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. Methods We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed. Results An episode of AMR was identified in 179 of 1,596 (11%) HT recipients and in 246 of 705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%) and eculizumab (0.4%). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13%). Thirty-three patients (16%) died after developing AMR. Patient and graft survival were lower for the AMR+ group. One- and 3-year survival after initial AMR diagnosis was 88% and 77%, respectively. Conclusions In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.

LanguageEnglish (US)
Pages1497-1504
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume35
Issue number12
DOIs
StatePublished - Dec 1 2016

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Cohort Studies
Outcome Assessment (Health Care)
Databases
Pediatrics
Transplants
Antibodies
Heart Transplantation
Therapeutics
Plasmapheresis
Intravenous Immunoglobulins
Biopsy
Immunotherapy
Survival
Graft Survival
Antibody Formation

Keywords

  • acute cellular rejection
  • antibody-mediated rejection
  • heart transplantation
  • humoral rejection
  • immunotherapy
  • pediatrics
  • rejection

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database : Incidence, therapies and outcomes. / Thrush, Philip T.; Pahl, Elfriede; Naftel, David C.; Pruitt, Elizabeth; Everitt, Melanie D.; Missler, Heather; Zangwill, Steven; Burch, Michael; Hoffman, Timothy M.; Butts, Ryan; Mahle, William T.

In: Journal of Heart and Lung Transplantation, Vol. 35, No. 12, 01.12.2016, p. 1497-1504.

Research output: Contribution to journalArticle

Thrush, PT, Pahl, E, Naftel, DC, Pruitt, E, Everitt, MD, Missler, H, Zangwill, S, Burch, M, Hoffman, TM, Butts, R & Mahle, WT 2016, 'A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database: Incidence, therapies and outcomes' Journal of Heart and Lung Transplantation, vol 35, no. 12, pp. 1497-1504. DOI: 10.1016/j.healun.2016.06.014
Thrush, Philip T. ; Pahl, Elfriede ; Naftel, David C. ; Pruitt, Elizabeth ; Everitt, Melanie D. ; Missler, Heather ; Zangwill, Steven ; Burch, Michael ; Hoffman, Timothy M. ; Butts, Ryan ; Mahle, William T./ A multi-institutional evaluation of antibody-mediated rejection utilizing the Pediatric Heart Transplant Study database : Incidence, therapies and outcomes. In: Journal of Heart and Lung Transplantation. 2016 ; Vol. 35, No. 12. pp. 1497-1504
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abstract = "Background Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. Methods We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed. Results An episode of AMR was identified in 179 of 1,596 (11\{%}) HT recipients and in 246 of 705 (35\{%}) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88\{%} and 82\{%} at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58\{%}), plasmapheresis (40\{%}), rituximab (40\{%}), bortezomib (11\{%}) and eculizumab (0.4\{%}). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13\{%}). Thirty-three patients (16\{%}) died after developing AMR. Patient and graft survival were lower for the AMR+ group. One- and 3-year survival after initial AMR diagnosis was 88\{%} and 77\{%}, respectively. Conclusions In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.",
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AU - Pruitt,Elizabeth

AU - Everitt,Melanie D.

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AU - Zangwill,Steven

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N2 - Background Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. Methods We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed. Results An episode of AMR was identified in 179 of 1,596 (11%) HT recipients and in 246 of 705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%) and eculizumab (0.4%). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13%). Thirty-three patients (16%) died after developing AMR. Patient and graft survival were lower for the AMR+ group. One- and 3-year survival after initial AMR diagnosis was 88% and 77%, respectively. Conclusions In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.

AB - Background Current knowledge of antibody-mediated rejection (AMR) after heart transplantation (HT) stems largely from adult data. Using the Pediatric Heart Transplant Study (PHTS) database, we report the incidence of AMR, describe treatment, and evaluate outcomes for treated AMR in children after HT. Methods We queried the PHTS database for patients <18 years of age undergoing primary HT between January 2010 and December 2014. An AMR episode was defined as either a biopsy consistent with pathologic AMR or a rejection event based on immunotherapy augmentation directed against antibody production. Biopsy data, treatment strategies and survival were analyzed. Results An episode of AMR was identified in 179 of 1,596 (11%) HT recipients and in 246 of 705 (35%) rejection episodes. AMR was diagnosed by biopsy in 182 of 246 episodes and by immunotherapy in 64 of 179 episodes. Mixed rejection was identified in 179. Freedom from AMR was 88% and 82% at 1 and 3 years, respectively. AMR therapies included intravenous immunoglobulin (IVIg) (58%), plasmapheresis (40%), rituximab (40%), bortezomib (11%) and eculizumab (0.4%). The most commonly used combination therapies included IVIg/plasmapheresis/rituximab (13%). Thirty-three patients (16%) died after developing AMR. Patient and graft survival were lower for the AMR+ group. One- and 3-year survival after initial AMR diagnosis was 88% and 77%, respectively. Conclusions In his study we report the largest experience of AMR in pediatric HT recipients. AMR was common and often occurred concurrently with acute cellular rejection. There is wide variability in the treatment of AMR. Short-term patient and graft outcomes were worse for those with treated AMR.

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