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Treatment of Acquired Factor VIII Deficiency With Rituximab

Treatment of Acquired Factor VIII Deficiency With Rituximab

At the 2000 American Society of Hematology meeting, we reported the successful treatment of a patient with acquired hemophilia using rituximab (Rituxan). This patient has required no therapy over the past year and has suffered no further hemorrhages. A June 2001 factor VIII level was 35%, and a factor VIII inhibitor level could not be analyzed due to the high level of factor VIII. Since then, three more patients with acquired factor VIII deficiency have received rituximab therapy at the University of Iowa, and are discussed below.

F.T. is a 78-year-old white female who required a 6-week hospitalization starting in March 2001 for treatment of soft-tissue hemorrhages associated with her hemophilia. She was treated with recombinant human coagulation factor VIIa (NovoSeven) and received four weekly doses of rituximab therapy at 375 mg/m²/wk. Prior to the rituximab therapy her factor VIII level was 2%, with a factor VIII inhibitor level of 56 Bethesda units. After therapy, she was admitted to the hospital for questionable gastrointestinal hemorrhage and developed an arthritis syndrome that required prednisone therapy. The patient has had no further hemorrhages. As of August 1, 2001, her factor VIII level was measured at 150%, with a factor VIII inhibitor level that could not be analyzed.

R.P. is a 73-year-old white male with a history of acquired factor VIII deficiency that had spontaneously resolved in 1996. In January 2001, recurrent soft-tissue bleeding occurred. In April 2001, he received a 4-week course of rituximab therapy (375 mg/m²/wk). His factor VIII level prior to therapy was 2%, with a factor VIII inhibitor level of 19 Bethesda units. Eight weeks after completion of the therapy, his factor VIII level had risen to 3% and his factor VIII inhibitor level had fallen to 2.8 Bethesda units.

N.Y. is a 79-year-old white female who was diagnosed with acquired hemophilia in January 2001. She required NovoSeven for soft-tissue hemorrhages. This patient is now 2 weeks out from completion of a 4-week course of rituximab therapy (375 mg/m²/wk). She has required no further therapy for hemorrhage, and a follow-up factor VIII level has not yet been obtained.

CONCLUSION: These four cases provide further evidence that rituximab appears to have a role in the treatment of acquired factor VIII deficiency. It is our opinion that the therapy is safe and effective, especially when compared to previous therapies (glucocorticoids and cytotoxics). Our conclusions are limited by the small number of patients, but they strongly suggest that further study is warranted.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

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