Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia.
The activity and safety profile of selective B-cell depletion with rituximab, an anti-CD20 monoclonal antibody, were evaluated in 10 patients with acquired hemophilia. Rituximab was given intravenously at the dose of 375 mg/m(2) once weekly for 4 consecutive weeks. Infusion-related side effects were observed in 3 patients but were of mild intensity and did not require discontinuation of treatment. Eight patients with Factor VIII (FVIII) inhibitor titers between 4 and 96 Bethesda units per milliliter (BU/mL) achieved a complete remission, which was defined as a return to normal FVIII activity and undetectable FVIII inhibitor titers. Two more patients with inhibitor levels greater than 100 BU/mL experienced only a partial transient decrease of the inhibitor after rituximab alone, but they achieved a complete response after being challenged with a combination of rituximab plus pulse intravenous cyclophosphamide. With a median follow-up of 28.5 months (range, 12-41 months), 3 patients have thus far relapsed. Retreatment with the monoclonal antibody at the same dose and schedule resulted in a new sustained response in all these patients. In conclusion, rituximab appears an effective and well-tolerated treatment for patients with acquired hemophilia and low inhibitor titers. A reinforcement of therapy with other agents seems to be required to achieve a full and durable response in those patients with high inhibitor levels.
Department of Medical Sciences, Regina Apostolorum Hospital, Via S. Francesco 50, 00041 Albano Laziale, Italy. roberto.stasi@uniroma2.it
Roberto
R
Stasi
Maurizio
M
Brunetti
Elisa
E
Stipa
Sergio
S
Amadori
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D005169:Factor VIII / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D000069283:Rituximab; D013997:Time Factors; D014842:von Willebrand Diseases / Q000188:drug therapy* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D005169:Factor VIII