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Blood, 15 June 2004, Vol. 103, No. 12, pp. 4424-4428.
Prepublished online as a Blood First Edition Paper on March 2, 2004; DOI 10.1182/blood-2003-11-4075.
Submitted December 1, 2003
Accepted February 21, 2004
Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia
Roberto Stasi*, Maurizio Brunetti, Elisa Stipa, and Sergio Amadori
Dept. of Medical Sciences, 'Regina Apostolorum' Hospital, Albano Laziale, Italy
Dept. of Hematology, University of Rome 'Tor Vergata', Rome, Italy
* Corresponding author; email: roberto.stasi{at}uniroma2.it.
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/m2 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 (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 >100 BU/ml experienced only a partial transient decrease of the inhibitor after rituximab alone, but achieved a complete response after being challenged with a combination of rituximab plus pulse intravenous cyclophosphamide. In responders, FVIII levels normalized, and the inhibitor became undetectable, between 3 and 12 weeks from the start of treatment. The B-cell counts fell to <30 x 106/L within 4 weeks from the first rituximab infusion in all patients, including non responders. Monitoring of serum immunoglobulin concentrations showed no significant changes in mean IgG or IgM levels after rituximab. With a median follow-up of 28.5 months (range, 12 to 41 months), three 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.
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