title: In vivo human B-cell subset recovery after in vivo depletion with rituximab, anti-human CD20 monoclonal antibody.
abstract: Rituximab, chimeric anti-human CD20 monoclonal antibody approved for B-cell lymphoma, depletes circulating B cells. Little data exist on its use for nonmalignant diseases or B-cell subset recovery after treatment. We hypothesized that rituximab may reduce panel reactive alloantibodies (PRA) in dialysis patients awaiting renal transplantation and performed a single-dose, dose-escalation phase 1 trial. Here we report changes in lymphocyte phenotypes in subjects treated with rituximab alone. Nine subjects, 44 +/- 10 years(Yr); (5 F, 4 M) received one dose (n=3) at 50, 150, or 375 mg/m(2) without other immunosuppression. Blood was collected before dosing and intervals thereafter. No significant changes in leukocytes, total or CD3(+) lymphocytes were noted. In all, there was CD19(+) depletion by day 2(D2) (12.0 +/- 5.6 cells/mm(3) vs. 181 +/- 137, D0; p<0.01) and CD20(+) (11.0 +/- 12.0 vs. 205 +/- 116, D0; p<0.01). At 6 months (mo), CD19(+) and CD20(+) remained low (51.1 +/- 42.2, p<0.05; 75.4 +/- 38.7, p<0.05, respectively) compared to D0. CD19(+)CD5(+) cells recovered more rapidly, returning to baseline by 6mo while B memory cells (CD19(+)CD27(+)) remained low (32.3 +/- 29.0) at 1Yr (7.5 +/- 4.5; p<0.001) and 2Yr (12.1 +/- 7.9; p<0.001) after treatment. We conclude that single dose rituximab ablates B cells in high PRA dialysis patients awaiting transplantation. B-cell ablation, particularly memory B cells, was long-lasting, lagging repopulation by CD5(+) B cells.
authors.affiliation: Indiana University School of Medicine, Department of Surgery, Indianapolis, IN 46202, USA. rsidner@iupui.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Sidner
authors.forename: Benita K
authors.initials: BK
authors.lastname: Book
authors.forename: Avinash
authors.initials: A
authors.lastname: Agarwal
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Bearden
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vieira
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D000069283:Rituximab; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab