Induction of Immune Tolerance in Patients with Hemophilia and Antibodies to Factor VIII by Combined Treatment with Intravenous IgG, Cyclophosphamide, and Factor VIII

TLDR

We have content for each. Let's aggregate. Background: Sentences with [Background, Purpose, Mechanism] first line includes background info: "The development of antibodies to factor VIII is a serious complication of the treatment of patients with hemophilia A." Also [Background] second line: "Because earlier treatment with factor VIII and cyclophosphamide or with factor VIII and IgG had been ineffective in these patients, our experience suggests that all three components of the protocol are required for the successful induction of tolerance to factor VIII." So background: context of antibodies complication and prior ineffective treatments. Combine into one sentence: "Antibody development against factor VIII is a serious complication of hemophilia A therapy, and prior regimens using factor VIII with cyclophosphamide or IgG alone have failed, underscoring the need for a combined approach." That covers. Purpose: The purpose is to induce immune tolerance.

Abstract

The development of antibodies to factor VIII is a serious complication of the treatment of patients with hemophilia A. We successfully induced immune tolerance in patients with such antibodies with a new treatment protocol, which combined factor VIII, cyclophosphamide, and high-dose intravenous IgG, followed by regular prophylactic treatment with factor VIII. This protocol has now been used in 11 patients with hemophilia A, of whom 9 had a strong antibody response. When the initial concentration of antibodies exceeded 3 Malmö inhibitor units (corresponding to about 10 Bethesda units) per milliliter, treatment was preceded by adsorption of antibody to protein A. After two to three weeks of the combined treatment, factor VIII coagulant antibodies had disappeared in 9 of the 11 patients; in 8 of these 9 patients the half-life of infused factor VIII had normalized. The tolerant state appears to be stable after a median of 30 months. Two patients did not respond to the treatment. Because earlier treatment with factor VIII and cyclophosphamide or with factor VIII and IgG had been ineffective in these patients, our experience suggests that all three components of the protocol are required for the successful induction of tolerance to factor VIII. (N Engl J Med 1988; 318:947–50.)