HLA desensitization with bortezomib in a highly sensitized pediatric patient

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 threedays of ECMO, followed by implantation of a Heartmate II LVAD. Within sixwk, the patient developed de novo class I IgG and C1q complement-fixing HLA antibodies with a cPRA of 100%. Two doses of IVIG (2g/kg) failed to reduce antibody levels, although two courses of a novel desensitization protocol consisting of rituximab (375mg/m(2)), bortezomib (1.3mg/m(2)x5 doses), and plasmapheresis reduced his cPRA to 0% and 87% by the C1q and IgG assays, respectively. He underwent heart transplantation nearly twomonths later. The patient is now >oneyr 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.