A new protocol for inhibitor elimination in high responding hemophilia A patients

Abstract number: P1610

Kreuz^* W., Linde^* R., Escuriola Ettingshausen^* C., Dunsch† D., Köhl† U., Figura† S., Klingebiel† T.

†Germany ^*University Hospital Frankfurt, Germany;

The treatment of hemophiliacs with high titer inhibitors represents a major challenge for each treating physician. Therefore immunotolerance is intended in order to enable regular treatment with factor (F) VIII or IX. However, some patients fail ITT. We report about a new therapy regimen in order to eliminate high titer FVIII inhibitors. A 14-year-old boy developed a high titer inhibitor against FVIII (maximum titer 1562 Bethesda Units, BU) at the age of 1 year. Immune tolerance induction according to the Bonn and the Malmö protocol failed. The patient imposed with recurrent severe bleedings, which were difficult to control with established therapeutic agents as rFVIIa and activated prothrombin complex. Immune tolerance induction was intended again using a monoclonal anti-CD20 antibody (MabThera™ Roche, 375 mg m^-2 body surface) as a single intravenous infusion followed by the administration of FVIII concentrate (100 IU kg^-1 bw twice daily). Additional immunosuppressive therapy was given (Cyclosporin A 3 mg kg^-1 bw po q2). After the administration of the anti-CD20 antibody the cell-surface antigen CD20 dropped to 0 and the inhibitor titer decreased continuously to 0,14 BU. Parallel the bleeding tendency diminished tremendously. The administration of MabThera™ was repeated when the inhibitor reappeared or when CD20 were again detectable. In the meantime type I inhibitor changed to type II. Then the inhibitor titer dropped to 0 BU constantly and recovery turned towards normal ranges (month 13). F VIII half-life is 7.5 h (month 28). During the whole treatment period no bleeding was observed. However, the patient acquired a hepatitis B infection and a pulmonary aspergillosis after catheter infection.

Conclusion  

The new therapeutic regimen seems to be a promising approach to eliminate inhibitors resistant to established ITT protocols. A pilot study is planned for high-responding inhibitor patients who failed ITT and impose with a severe bleeding tendency.