title: Bortezomib use in a pediatric cardiac transplant center.
abstract: Data are limited on the efficacy and safety of bortezomib for the treatment of AMR following OHT for pediatric acquired or CHD. Retrospective chart review identified patients who received bortezomib for acute (n = 3, within two wk of diagnosis) and chronic (n = 1, three months after diagnosis) AMR or as part of a desensitization regimen (n = 1). Bortezomib was associated with a 3-66% reduction in class I DSA and a 7-82% reduction in class II DSA. Two of the three acute AMR cases resolved by the first follow-up biopsy. Two patients with AMR resolution are currently well. One patient developed a second episode of AMR, which was unresponsive to bortezomib therapy and required retransplantation for progressive coronary allograft vasculopathy. One patient died shortly after the third cycle from multi-organ failure. The desensitization patient showed transient HLA reduction with two cycles, but died five months after transplant from sepsis. Complications included infection (3/5), peripheral neuropathy (2/5), AKI (2/5), and thrombocytopenia (3/5). Adverse events appear more common in critically ill patients. Bortezomib therapy resulted in variable DSA reduction and AMR resolution in AMR in OHT secondary to pediatric acquired or CHD.
authors.affiliation: Children's Hospital of Michigan, Detroit, MI, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Zinn
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: L'Ecuyer
authors.forename: Omar R
authors.initials: OR
authors.lastname: Fagoaga
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Aggarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood; D001706:Biopsy; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006330:Heart Defects, Congenital / Q000601:surgery*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011719:Pyrazines; D000069286:Bortezomib
keywords: antibody-mediated rejection; bortezomib; congenital heart disease; orthotopic heart transplantation