Induced Tolerance in Hemophilia Patients with Antibodies against IX:C

Abstract

Two patients with severe hemophilia B complicated with antibodies against factor IX were treated 13 and 10 times, respectively, with high doses of factor IX concentrate in combination with cyclophosphamide over a period of 10 yr. During this treatment a lowering of the anamnestic response was observed over the years. Both patients have now been treated with factor IX and hydrocortisone but no cyclophosphamide to find if real tolerance was induced. One patient received such treatment 3 times and the other once. Their inhibitor titer following these treatment episodes never exceeded 0.3 U/ml (.apprx. 0.9 BU[Bethesda Unit]/ml) and 0.9 U/ml (.apprx. 2.7 BU/ml) which is of the same order of magnitude as following the combined treatment (factor IX, hydrocortisone and cyclophosphamide). Evidently, these patients were converted from high responders (10- to 100-fold increase in the inhibitor titer on the original treatment with factor IX and hydrocortisone) into low responders showing a reasonable inhibitor increase after treatment with factor IX and hydrocortisone but no cyclophosphamide.