title: Rituximab and intravenous immune globulin for desensitization during renal transplantation.
abstract: BACKGROUND
  Few options for transplantation currently exist for patients highly sensitized to HLA. This exploratory, open-label, phase 1-2, single-center study examined whether intravenous immune globulin plus rituximab could reduce anti-HLA antibody levels and improve transplantation rates.
  
  
  METHODS
  Between September 2005 and May 2007, a total of 20 highly sensitized patients (with a mean [+/-SD] T-cell panel-reactive antibody level, determined by use of the complement-dependent cytotoxicity assay, of 77+/-19% or with donor-specific antibodies) were enrolled and received treatment with intravenous immune globulin and rituximab. We recorded rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, serum creatinine values, adverse events and serious adverse events, and immunologic factors.
  
  
  RESULTS
  The mean panel-reactive antibody level was 44+/-30% after the second infusion of intravenous immune globulin (P<0.001 for the comparison with the pretreatment level). At study entry, the mean time on dialysis among recipients of a transplant from a deceased donor was 144+/-89 months (range, 60 to 324). However, the time to transplantation after desensitization was 5+/-6 months (range, 2 to 18). Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean serum creatinine level was 1.5+/-1.1 mg per deciliter (133+/-97 micromol per liter), and the mean survival rates of patients and grafts were 100% and 94%, respectively. There were no infusion-related adverse events or serious adverse events during the study. Long-term monitoring for infectious complications and neurologic problems revealed no unanticipated events.
  
  
  CONCLUSIONS
  These findings suggest that the combination of intravenous immune globulin and rituximab may prove effective as a desensitization regimen for patients awaiting a transplant from either a living donor or a deceased donor. Larger and longer trials are needed to evaluate the clinical efficacy and safety of this approach. (ClinicalTrials.gov number, NCT00642655.)
authors.affiliation: Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles 90048, USA. ashley.vo@cshs.org
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Vo
authors.forename: Marina
authors.initials: M
authors.lastname: Lukovsky
authors.forename: Mieko
authors.initials: M
authors.lastname: Toyoda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wang
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lai
authors.forename: Alice
authors.initials: A
authors.lastname: Peng
authors.forename: Rafael
authors.initials: R
authors.lastname: Villicana
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19 / Q000097:blood; D018951:Antigens, CD20 / Q000276:immunology*; D003404:Creatinine / Q000097:blood; D003888:Desensitization, Immunologic / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D015996:Survival Rate
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab; D003404:Creatinine