Faculty Collaboration Database

Rituximab for the treatment of patients with very high-titre acquired factor VIII inhibitors refractory to conventional chemotherapy. Haemophilia 2007 Jan;13(1):46-50

Date

01/11/2007

Pubmed ID

17212724

DOI

10.1111/j.1365-2516.2006.01342.x

Scopus ID

2-s2.0-33845741137 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

Acquired factor VIII (FVIII) inhibitors are a rare cause of coagulopathy which are associated with a high mortality rate. Treatment of bleeding episodes is often difficult and may vary with the degree of titre elevation. Individuals with very high-titre antibodies [>100 Bethesda units mL(-1) (BU)] may have difficulty achieving a complete sustained remission and, consequently, various treatments including immunosuppression, cytotoxic chemotherapy and plasmapheresis have been reported. Rituximab is an anti-CD20 monoclonal antibody which has demonstrated efficacy in the treatment of individuals with acquired FVIII inhibitors, however there is limited data in the subgroup of patients with inhibitor titres >100 BU. In this study, we present four patients with acquired FVIII inhibitor titres >100 BU who were resistant to initial therapy with cyclophosphamide, vincristine and prednisone. The patients' inhibitor titres ranged from 249 BU mL(-1) to 725 BU mL(-1) and all received 4 weekly infusions of rituximab at 375 mg m(-2). Each patient partially responded to rituximab therapy with an improvement in inhibitor titres and FVIII activity, however, three of the four patients relapsed thereafter. The individual who did not relapse achieved a partial response for 13 months and then died of causes unrelated to her coagulopathy. We conclude that in patients with acquired FVIII inhibitors and titres >100 BU, treatment with rituximab alone is effective but not sufficient to achieve a sustained response. Rituximab in combination with other therapies may provide a better result in this high-risk population.

Author List

Field JJ, Fenske TS, Blinder MA

Authors

Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Joshua J. Field MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Murine-Derived
Antigens, CD20
Blood Coagulation Factor Inhibitors
Cyclophosphamide
Drug Administration Schedule
Drug Therapy, Combination
Factor VIII
Female
Hemophilia A
Hemorrhage
Humans
Immunologic Factors
Immunosuppressive Agents
Isoantibodies
Male
Middle Aged
Prednisone
Recurrence
Rituximab
Time Factors
Treatment Failure
Vincristine