Chesney Castleberry1, Elizabeth Pruitt2, Rebecca Ameduri3, Kenneth Schowengerdt4, Erik Edens5, Nancy Hagin6, James K Kirklin2, David Naftel2, Simon Urschel7. 1. Department of Pediatric Cardiology, Washington University in St. Louis, St. Louis, Missouri, USA. Electronic address: castleberry_c@kids.wustl.edu. 2. Department of Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA. 3. Department of Pediatric Cardiology, University of Minnesota, Minneapolis, Minnesota, USA. 4. Department of Pediatric Cardiology, Cardinal Glennon Children's Hospital, St. Louis, Missouri, USA; Department of Cardiology, Saint Louis University School of Medicine, St. Louis, Missouri, USA. 5. Department of Pediatrics, Division of Pediatric Cardiology, University of Iowa, Iowa City, Iowa, USA. 6. Department of Pediatric Cardiology, Washington University in St. Louis, St. Louis, Missouri, USA. 7. Department of Cardiac Sciences, University of Alberta, Edmonton, Alberta, Canada.
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.
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.
Authors: Martin Schweiger; Andreas Zuckermann; Andres Beiras-Fernandez; Michael Berchtolld-Herz; Udo Boeken; Jens Garbade; Stephan Hirt; Manfred Richter; Arjang Ruhpawar; Jan Dieter Schmitto; Felix Schönrath; Rene Schramm; Uwe Schulz; Markus J Wilhelm; Markus J Barten Journal: Ann Transplant Date: 2018-05-15 Impact factor: 1.530