Combination Immunosuppressive Therapy After Factor VIII Infusion for Acquired Factor VIII Inhibitor

Study Objective: To evaluate the effectiveness of combined cyclophosphamide, vincristine, and prednisone (CVP) therapy after antigenic stimulation with factor VIII in the eradication of factor VIII inhibitor.

Design: Factor VIII activity and inhibitor titer were measured before and after FVIII-CVP therapy and patients with factor VIII inhibitor were followed for at least 2 years.

Setting: The first course of therapy was carried out in the hospital when nonhemophiliac patients were admitted for bleeding. Otherwise, treatment was administered at the outpatient clinic.

Patients: From 1975 to 1986 we studied 12 nonhemophiliac and 5 hemophiliac patients with factor VIII inhibitor treated with FVIII-CVP and followed at our clinic.

Intervention: Patients were infused with one dose of factor VIII concentrate, 50 to 100 U/kg body weight, followed by cyclophosphamide, 500 mg on day 1 and 200 mg/d on days 2 to 5; vincristine, 2 mg on day 1; and prednisone, 100 mg/d on days 1 to 5. This regimen was repeated every 3 to 4 weeks.

Results: Of 12 nonhemophiliac patients, 11 responded after 1 to 3 courses of FVIII-CVP with complete disappearance of the inhibitor without recurrence. Among 5 patients with hemophilia who were given 3 to 8 courses, only 1 patient responded with a transient disappearance of inhibitor. Mild neutropenia and infection occurred in 3 patients and required antibiotic treatment.

Conclusion: Factor VIII-CVP therapy is highly effective in the eradication of factor VIII inhibitor in nonhemophiliac patients but not in patients with hemophilia.