An alternative immune tolerance induction therapy for patients with inhibitors in hemophilia A

W.-A. Hassenpflug, J. Schrum, R. Dittmer, R. Schneppenheim (Hamburg, Germany)

Pediatric - Hemostasis
Date: 16.02.2017,
Time: 08:00 - 09:15

Objective: The development of inhibitory antibodies is considered the most severe complication in hemophilia treatment today. About 30% of hemophilia A patients develop inhibitors. Despite the treatment options that bypassig agents provide in these patients the eradication of the inhibitor remains the preferred treatment strategy. One successful protocol (Bonn protocol) uses high doses of factor VIII to induce immune tolerance. If this protocol fails treatment options are scarce. We treated two patients with hemophilia A who failed to respond to the Bonn protocol and aimed at developing an alternative regimen for inhibitor eradication.

Methods: The first patient had a very high inhibitor titer of 20.000 Bethesda units and needed an urgent neurosurgical procedure for Moyamoya syndrome. The second patient suffered from frequent joint bleedings despite continuous treatment with bypassing agents. In order to eradicate the inhibitors in these patients we combined classical high dose factor VIII treatment (2x 100 IE/kg bw) with immunosuppression (4x Rituximab 375mg/kg bw/week, mycophenolat mofetil 2x 300mg/m^2, steroids and immunoglobulins). The combination of different immunosuppressive drugs aimed at suppressing both B cells and T cells.

Results: Both patients showed a rapid decrease of the inhibitor activity. In the first patient neurosurgical palliation of the Moyamoya syndrome could be performed successfully under substitution with regular factor VIII concentrate after two cycles of our protocol. In the second patient spontaneous bleeding episodes stopped and joint status improved. After more than one year follow-up both patients show negative inhibitor titers and a good recovery but reduced half life of substituted factor VIII. We did not observe any adverse effects of the immunosuppressive therapy. In particular, there was no increase in infections.

Conclusion: In our patients the alternative immune tolerance induction as outlined above was effective and safe. Whether this protocol is suitable for other patients who failed classical immune tolerance induction and long-time follow-up is currently under investigation.