HLA desensitization with bortezomib in a highly sensitized pediatric patient

Pediatr Transplant. 2014 Dec;18(8):E280-2. doi: 10.1111/petr.12347. Epub 2014 Sep 1.


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.

Keywords: bortezomib; desensitization; human leukocyte antigen antibodies; pediatric heart transplant.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Cardiomyopathy, Dilated / surgery*
  • Child
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • HLA Antigens / immunology*
  • Heart Transplantation*
  • Humans
  • Immunologic Factors / therapeutic use
  • Isoantibodies / immunology
  • Male
  • Plasmapheresis
  • Proteasome Inhibitors / therapeutic use*
  • Pyrazines / therapeutic use*
  • Rituximab
  • Transplantation Conditioning / methods*


  • Antibodies, Monoclonal, Murine-Derived
  • Boronic Acids
  • HLA Antigens
  • Immunologic Factors
  • Isoantibodies
  • Proteasome Inhibitors
  • Pyrazines
  • Rituximab
  • Bortezomib