Combined Upfront Immunosuppression for Acquired Hemophilia A

Acquired haemophilia A (AHA) is an extremely rare autoimmune disorder caused by autoantibodies to coagulation factor VIII and characterized by life-threatening bleeding within soft tissues and vital organs. Supportive therapy for bleed control and immunosuppressive therapy remain the backbone of treatment, but there is no consensus about the best immunosuppressive therapy. Most regimens include upfront steroids followed by other immunosuppressive agents (e.g., rituximab, cyclophosphamide, cyclosporine) when steroids fail.

In an attempt to reduce steroid exposure and toxicity, investigators in Hungary instituted an upfront, combined, pulse-dosed immunosuppressive treatment protocol in 2009. Now, they report outcomes for the first 32 patients (median age, 77) treated with the protocol at two institutions from 2009 to 2020. The CyDRi protocol consists of cyclophosphamide (1000 mg on days 1 and 22), dexamethasone (40 mg on days 1, 8, 15, and 22), and rituximab (100 mg on days 1, 8, 15, and 22). The same regimen was used to treat relapses.

All patients received at least one cycle of CyDRi. At a median follow-up of 780 days, the rate of complete remission was 96.9% and overall survival was 90.6%. The relapse rate was 6.3% (2 patients had 5 relapses, all responded to CyDRi). Median time to bleeding control was 15.5 days and median time to complete remission was 77 days. Regimen-related toxicity was minimal.