Risk stratification to determine the impact of induction therapy on survival, rejection and adverse events after pediatric heart transplant

A multi-institutional study

Chesney Castleberry, Elizabeth Pruitt, Rebecca K Ameduri, Kenneth Schowengerdt, Erik Edens, Nancy Hagin, James K. Kirklin, David Naftel, Simon Urschel

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. Methods: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25% risk of predicted mortality were defined as high risk (HR) and the bottom 75% as low risk (LR). Results: Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups. Conclusions: Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.

Original languageEnglish (US)
Pages (from-to)458-466
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume37
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Pediatrics
Transplants
Survival
Interleukin-2 Receptors
Cardiomyopathies
Therapeutics
Mortality
Heart Transplantation
Infection
Anti-Idiotypic Antibodies
Heart Diseases
Transplantation
Databases
Lymphocytes

Keywords

  • PTLD
  • induction
  • interleukin-2 receptor antagonists
  • pediatric heart transplantation
  • rejection
  • thymoglobulin
  • vasculopathy

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Risk stratification to determine the impact of induction therapy on survival, rejection and adverse events after pediatric heart transplant : A multi-institutional study. / Castleberry, Chesney; Pruitt, Elizabeth; Ameduri, Rebecca K; Schowengerdt, Kenneth; Edens, Erik; Hagin, Nancy; Kirklin, James K.; Naftel, David; Urschel, Simon.

In: Journal of Heart and Lung Transplantation, Vol. 37, No. 4, 01.04.2018, p. 458-466.

Research output: Contribution to journalArticle

Castleberry, Chesney ; Pruitt, Elizabeth ; Ameduri, Rebecca K ; Schowengerdt, Kenneth ; Edens, Erik ; Hagin, Nancy ; Kirklin, James K. ; Naftel, David ; Urschel, Simon. / Risk stratification to determine the impact of induction therapy on survival, rejection and adverse events after pediatric heart transplant : A multi-institutional study. In: Journal of Heart and Lung Transplantation. 2018 ; Vol. 37, No. 4. pp. 458-466.
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abstract = "Background: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. Methods: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25{\%} risk of predicted mortality were defined as high risk (HR) and the bottom 75{\%} as low risk (LR). Results: Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups. Conclusions: Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.",
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AU - Castleberry, Chesney

AU - Pruitt, Elizabeth

AU - Ameduri, Rebecca K

AU - Schowengerdt, Kenneth

AU - Edens, Erik

AU - Hagin, Nancy

AU - Kirklin, James K.

AU - Naftel, David

AU - Urschel, Simon

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N2 - Background: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. Methods: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25% risk of predicted mortality were defined as high risk (HR) and the bottom 75% as low risk (LR). Results: Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups. Conclusions: Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.

AB - Background: Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk. Methods: The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25% risk of predicted mortality were defined as high risk (HR) and the bottom 75% as low risk (LR). Results: Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups. Conclusions: Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.

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KW - interleukin-2 receptor antagonists

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KW - rejection

KW - thymoglobulin

KW - vasculopathy

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