title: Immune tolerance with rituximab in congenital haemophilia with inhibitors: a systematic literature review based on individual patients' analysis.
abstract: Rituximab, a monoclonal antibody against the pan B-cell antigen CD20, has been successfully used in both adults and children for the management of malignant and non-malignant immune-mediated disorders including acquired haemophilia. On the basis of this positive experience, a number of investigators have recently used this agent in patients with congenital haemophilia and inhibitors refractory to first-line treatments. After a careful electronic and hand search, we have collected 29 studies that included 49 cases. A durable complete remission was obtained in 53% of the cases and no severe adverse events related to rituximab were recorded. A multivariate analysis applied to individual patients' data identified the diagnosis of a mild/moderate haemophilia and the concomitant treatment with factor VIII concentrates and immunosuppression agents as covariates associated with an increased response to rituximab. Large prospective randomized studies with an adequate follow-up are needed to confirm these preliminary findings.
authors.affiliation: Immunohematology and Transfusion Center, City Hospital of Parma, Parma, Italy. massimo.franchini@azosp.vr.it
authors.forename: M
authors.initials: M
authors.lastname: Franchini
authors.forename: C
authors.initials: C
authors.lastname: Mengoli
authors.forename: G
authors.initials: G
authors.lastname: Lippi
authors.forename: G
authors.initials: G
authors.lastname: Targher
authors.forename: M
authors.initials: M
authors.lastname: Montagnana
authors.forename: G L
authors.initials: GL
authors.lastname: Salvagno
authors.forename: M
authors.initials: M
authors.lastname: Zaffanello
authors.forename: M
authors.initials: M
authors.lastname: Cruciani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology; D006467:Hemophilia A / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007518:Isoantibodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D000069283:Rituximab; D005169:Factor VIII