title: Bortezomib for refractory autoimmunity in pediatrics.
abstract: Therapy of refractory autoimmunity remains challenging. In this study, we evaluated the therapeutic effect of bortezomib, a proteasome inhibitor, by targeting plasma cells in 7 patients (median age, 9.9 years). Four doses of bortezomib were administered at a dose of 1.3 mg/m(2) intravenously (n = 6) or subcutaneously (n = 1) every 72 hours. Bortezomib was administered at a median of 120 days from laboratory confirmation of autoantibodies. All patients had failed 2 or more standard therapies. Rituximab was administered on the first day if B cells were present, and all patients received plasmapheresis 2 hours before bortezomib administration. Six patients experienced resolution of cytopenias. Two of 6 patients experienced recurrence of cytopenias after initial response. Adverse effects include nausea (n = 1), thrombocytopenia (n = 2), Clostridium difficile colitis (n = 1)), febrile neutropenia (n = 1), and cellulitis at the subcutaneous injection site (n = 1). Our experience suggests that bortezomib may be beneficial in the treatment of refractory autoimmunity in children.
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: Pooja.khandelwal@cchmc.org.
authors: Pooja
authors: P
authors: Khandelwal
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Stella M
authors: SM
authors: Davies
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Michael S
authors: MS
authors: Grimley
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Michael B
authors: MB
authors: Jordan
authors: Platelet & Neutrophil Immunology Laboratory, Blood Center of Wisconsin, Milwaukee, Wisconsin.
authors: Brian R
authors: BR
authors: Curtis
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Sonata
authors: S
authors: Jodele
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Rebecca
authors: R
authors: Marsh
authors: Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors: Alexandra H
authors: AH
authors: Filipovich
mesh_terms: D000293:Adolescent; D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015551:Autoimmunity / Q000187:drug effects*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009503:Neutropenia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010956:Plasmapheresis; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D012189:Retrospective Studies; D000069283:Rituximab; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib
keywords: Autoimmune cytopenias; Bortezomib; Proteasome inhibition; Refractory autoimmunity