title: Randomized controlled pilot study of B cell-targeted induction therapy in HLA sensitized kidney transplant recipients.
abstract: Optimal induction regimens for patients at high risk for antibody and/or cell-mediated rejection have not been established. This pilot, prospective, randomized study evaluated addition of B cell/plasma cell-targeting agents to T cell-based induction with rabbit antithymocyte globulin (rATG) in high immunologic risk renal transplant recipients. Patients were randomized to induction with rATG, rATG + rituximab, rATG + bortezomib or rATG + rituximab + bortezomib. Inclusion criteria were: (1) current cytotoxic panel reactive antibody (PRA) ≥20% or peak cytotoxic PRA ≥50% or (2) T or B cell positive flow crossmatch with donor-specific antibody (DSA) or (3) historical positive serologic or cytotoxic crossmatch or DSA to donor or (4) prior allograft loss with more than one acute rejection. Median overall follow-up was 496 days: 1-year and overall acute rejection were 25% and 27.5%, and 25% of patients developed de novo DSA within 1 year. One-year and overall patient survival were 97.5% and 92.5%, and 1-year and overall death-censored allograft survival were 97.5% and 95%. Renal allograft function posttransplant was similar among all arms. Eight of nine cases of peripheral neuropathy were mild, whereas one case was moderate and required a narcotic prescription. In conclusion, addition of rituximab and/or bortezomib to rATG induction has an acceptable safety/toxicity profile in a high immunologic risk renal transplant population.
authors.affiliation: Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH.
authors.forename: N S
authors.initials: NS
authors.lastname: Ejaz
authors.forename: A R
authors.initials: AR
authors.lastname: Shields
authors.forename: R R
authors.initials: RR
authors.lastname: Alloway
authors.forename: B
authors.initials: B
authors.lastname: Sadaka
authors.forename: A L
authors.initials: AL
authors.lastname: Girnita
authors.forename: G
authors.initials: G
authors.lastname: Mogilishetty
authors.forename: M
authors.initials: M
authors.lastname: Cardi
authors.forename: E S
authors.initials: ES
authors.lastname: Woodle
mesh_terms: D000328:Adult; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000166:cytology*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011183:Postoperative Complications; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D011817:Rabbits; D051437:Renal Insufficiency / Q000276:immunology* / Q000628:therapy; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000961:Antilymphocyte Serum; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D011719:Pyrazines; D000069283:Rituximab; D000069286:Bortezomib
keywords: B cells; HLA antibodies; highly sensitized; kidney transplantation