title: 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody.
abstract: We previously showed that bortezomib (BTZ) partially depletes plasma cells, yet has limited efficacy for desensitization in kidney transplant candidates when up to 16 doses is given.
  
  
  
  This study aimed to determine the safety and efficacy of 32 doses of BTZ (1.3 mg/m of body surface area) in 10 highly sensitized kidney transplant candidates with alloantibodies against their intended living donor.
  
  
  
  Dose reduction was needed in 2 patients and 2 others completely discontinued therapy for adverse events. Anti-HLA antibodies mean fluorescence intensity (MFI) values were stable prior to BTZ (P = 0.96) but decreased after therapy (mean decrease of 1916 [SE, 425] MFI, P < 0.01). No patient developed a negative crossmatch against their original intended donor, and the calculated panel-reactive antibodies based on MFI of 2000, 4000, and 8000 was unchanged in all patients.
  
  
  
  These data suggest that 32 doses of BTZ monotherapy was not well tolerated and resulted in only a modest reduction in anti-HLA antibodies.
authors.affiliation: 1 Division of Transplantation Surgery, Mayo Clinic, Rochester, MN. 2 Division of Transfusion Medicine, Mayo Clinic, Rochester, MN. 3 Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. 4 Division of Health Sciences Research, Mayo Clinic, Rochester, MN. 5 Division of Transplantation Surgery and von Liebig Transplant Center, Mayo Clinic, Rochester, MN.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Moreno Gonzales
authors.forename: Manish J
authors.initials: MJ
authors.lastname: Gandhi
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Schinstock
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Moore
authors.forename: Byron H
authors.initials: BH
authors.lastname: Smith
authors.forename: Nong Y
authors.initials: NY
authors.lastname: Braaten
authors.forename: Mark D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D000069286:Bortezomib / Q000008:administration & dosage* / Q000009:adverse effects; D003888:Desensitization, Immunologic / Q000379:methods*; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069286:Bortezomib