title: Failure of rituximab to induce immune tolerance in a boy with severe haemophilia A and an alloimmune factor VIII antibody: a case report and review of the literature.
abstract: We report the use of rituximab (MabThera); Roche Grenzach-Wyhlen, Germany) in a 6-year-old boy with severe haemophilia A and a high titre alloimmune factor VIII (FVIII) antibody, which had failed to respond to standard immune tolerance therapy. Rituximab was administered in 4 weekly doses with concurrent high-dose i.v. immunoglobulin (Flebogamma); Grifols, Barcelona, Spain) followed by daily high-dose recombinant FVIII concentrate (Recombinate); Baxter, CA, USA). Despite a fall in CD20 positive cell count to undetectable levels the inhibitor persisted. We discuss the possible reasons for failure of immune tolerance induction and review the literature concerning the use of rituximab for this indication.
authors.affiliation: Newcastle Haemophilia Comprehensive Care Centre, Newcastle Hospitals NHS Trust, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK. tbiss@dsl.pipex.com
authors.forename: T T
authors.initials: TT
authors.lastname: Biss
authors.forename: M R
authors.initials: MR
authors.lastname: Velangi
authors.forename: J P
authors.initials: JP
authors.lastname: Hanley
mesh_terms: D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D005167:Factor VII / Q000276:immunology / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology* / Q000627:therapeutic use; D015942:Factor VIIa; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007223:Infant; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D000069283:Rituximab; D017211:Treatment Failure
chemical_list: D000906:Antibodies; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D011994:Recombinant Proteins; D000069283:Rituximab; C078147:F8 protein, human; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa