title: HLA desensitization with bortezomib in a highly sensitized pediatric patient.
abstract: The proteasome inhibitor bortezomib has been used with variable success in the treatment of AMR following heart transplant. There is limited experience with this agent as a pretransplant desensitizing therapy. We report a case of successful HLA desensitization with a bortezomib-based protocol prior to successful heart transplantation. A nine-yr-old boy with dilated cardiomyopathy, not initially sensitized to HLA (cPRA of zero), required three days of ECMO, followed by implantation of a Heartmate II LVAD. Within six wk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2 g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375 mg/m(2) ), bortezomib (1.3 mg/m(2)  × 5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly two months later. The patient is now >one yr post-transplant, is free of both AMR and ACR, and has no detectable donor-specific antibodies by IgG or C1q. Proteasome inhibition with bortezomib and plasmapheresis may be an effective therapy for HLA desensitization pretransplant.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: May
authors.forename: Justin
authors.initials: J
authors.lastname: Yeh
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Maeda
authors.forename: Dolly B
authors.initials: DB
authors.lastname: Tyan
authors.forename: Sharon
authors.initials: S
authors.lastname: Chen
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kaufman
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: David N
authors.initials: DN
authors.lastname: Rosenthal
authors.forename: Seth A
authors.initials: SA
authors.lastname: Hollander
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D002311:Cardiomyopathy, Dilated / Q000601:surgery*; D002648:Child; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D010956:Plasmapheresis; D061988:Proteasome Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D000069283:Rituximab; D019172:Transplantation Conditioning / Q000379:methods*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001897:Boronic Acids; D006680:HLA Antigens; D007155:Immunologic Factors; D007518:Isoantibodies; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib
keywords: bortezomib; desensitization; human leukocyte antigen antibodies; pediatric heart transplant