BACKGROUND: There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens-sensitized pediatric HTx recipients. METHODS AND RESULTS: We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; > 10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis +/- intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post-HTx. Seven had early acute cellular rejection (> or = ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients > 6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy. CONCLUSIONS: Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell-directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes.
BACKGROUND: There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens-sensitized pediatric HTx recipients. METHODS AND RESULTS: We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; > 10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis +/- intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post-HTx. Seven had early acute cellular rejection (> or = ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients > 6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy. CONCLUSIONS: Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell-directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes.
Authors: 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 Diop; Jonah Odim; Steven A Webber Journal: Am J Transplant Date: 2018-03-23 Impact factor: 8.086
Authors: Christopher S Almond; Kimberlee Gauvreau; Ravi R Thiagarajan; Gary E Piercey; Elizabeth D Blume; Leslie B Smoot; Francis Fynn-Thompson; Tajinder P Singh Journal: Circulation Date: 2010-04-19 Impact factor: 29.690
Authors: Jon Kobashigawa; Maria G Crespo-Leiro; Stephan M Ensminger; Hermann Reichenspurner; Annalisa Angelini; Gerald Berry; Margaret Burke; Lawrence Czer; Nicola Hiemann; Abdallah G Kfoury; Donna Mancini; Paul Mohacsi; Jignesh Patel; Naveen Pereira; Jeffrey L Platt; Elaine F Reed; Nancy Reinsmoen; E Rene Rodriguez; Marlene L Rose; Stuart D Russell; Randy Starling; Nicole Suciu-Foca; Jose Tallaj; David O Taylor; Adrian Van Bakel; Lori West; Adriana Zeevi; Andreas Zuckermann Journal: J Heart Lung Transplant Date: 2011-03 Impact factor: 10.247
Authors: Brian Feingold; Seo Young Park; Diane M Comer; Charity G Moore; Steven A Webber; Cindy L Bryce Journal: J Heart Lung Transplant Date: 2012-11-13 Impact factor: 10.247
Authors: Kevin P Daly; Stephanie F Chandler; Christopher S Almond; Tajinder P Singh; Helen Mah; Edgar Milford; Gregory S Matte; Heather J Bastardi; John E Mayer; Francis Fynn-Thompson; Elizabeth D Blume Journal: Pediatr Transplant Date: 2013-08-06