Induction of immune tolerance in patients with hemophilia A and inhibitors.

Infusions of factor VIII at 50-100 U/kg were administered "on demand" for bleeding episodes, or once weekly, in eight patients (aged 3-20 years) with hemophilia A and historically high titer inhibitors to factor VIII. Inhibitors were eliminated and immunologic tolerance to factor VIII occurred in five of the eight patients within 5-31 months. Four patients had minimal anamnestic responses upon starting factor VIII infusions. One patient, who continued on weekly factor VIII after appearance of the inhibitor, had a continued rise in titer for 10 weeks, followed by a gradual decrease and elimination of the inhibitor at 24 months. Three patients had marked anamnestic rises in the inhibitor levels (204-2150 BU) at the start of the factor VIII infusions, followed by a slow fall and eventual suppression of the inhibitor titers to less than 15 BU. The administration of IgG, cyclophosphamide, and prednisone was only partially successful at enhancing inhibitor suppression in two of the highest responding patients. This less intensive factor VIII infusion program appeared as effective, better tolerated, and less costly than other more intensive protocols utilizing daily factor VIII for inducing immune tolerance in hemophilia patients with inhibitors.