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Presenter: Luis, Morales-Buenrostro, Mexico City, Mexico
Authors: Morales-Buenrostro L., Leyva S., Marino-Vazquez L., Vega-Vega O., Cantu G.
LABORATORY IMMUNOLOGY AND KIDNEY TRANSPLANTATION
L.E. Morales-buenrostro1, S.A. Leyva2, L.A. Marino-vazquez2, O. Vega-vega2, G. Cantu3
1Nephrology And Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City/MEXICO, 2Nephrology, Instituto Nacional de Ciencias Médicas y Nutrición SZ, Mexico City/MEXICO, 3Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición SZ, Mexico City/MEXICO
Body: Background. Bortezomib is a proteosomal inhibitor currently in use for treatment of humoral response in transplantation and autoimmune disease because it targets the mature antibody-producing plasma cell. The aim of this study is to communicate our clinical experience with bortezomib use as rejection therapy. Methods. Fifteen episodes of antibody-mediated rejection (AMR) in 14 kidney transplant recipients (KTR) were treated with bortezomib (1.3 mg/m2BS) in 3 different schemes: 1)Bortezomib 1 dose + Rituximab 500 mg in 3 AMR events. 2) Bortezomib 4 doses + 3 plasmapheresis (PP) sessions (1.5 plasma exchange each) in 5 AMR events. 3) Bortezomib 4 doses + 3 PP + Rituximab in 7 AMR events. Additionally, 3 methylprednisolone pulses were used in 13 events. Monitoring included: serial HLA donor-specific-antibody (DSA) measures, SCr, repeated allograft biopsy after treatment, and evaluation of any adverse event. Results. Fourteen KTR received bortezomib for AMR. Bortezomib scheme 1 provided complete clinical response (SCr returned to baseline level) and sustained effect in 2/3 cases and transient response in 1/3; however, without significant reduction in DSA levels in none of them. Bortezomib scheme 2 showed complete rejection resolution, and a 75% reduction DSA levels in 3 events (posttreatment HLA-DSA are pending in 2 events); Bortezomib scheme 3 gave good clinical rejection response, and we found DSA levels reduction at less 50% in 4 events, a null response in 1 event (after treatment HLA-DSA measure are pending in 2 events). The Bortezomib related toxicities were: transient mild thrombocytopenia, diarrhea, moderate-severe neuropathy (in one patient), and 1 case with mild confirmed Influenza A/H1N1. Conclusions. Bortezomib therapy with different schemes provided effective treatment of AMR in 13/15 events, with minimal toxicity. The mean time DSA will remain suppressed along with sustained clinical response, and the best Bortezomib combination are issues that must be clarify in a multicenter, randomized, controlled, clinical study. Even though the limited number of AMR event treated, it was observed that patients treated with four doses of Bortezomib + plasmapheresis showed an important HLA-DSA reduction in MFI levels.
Disclosure: All authors have declared no conflicts of interest.
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