Immune tolerance induction and the treatment of hemophilia. Malmö protocol update.
The Malmö protocol for immune tolerance induction includes high doses of Factor VIII/IX, intravenous IgG and cyclophosphamide. If the inhibitor titer exceeds 10 Bethesda units at start, extracorporeal adsorption of IgG is performed using protein A. The protocol sometimes has to be repeated. A successful response may occur within a few weeks. In hemophilia A the success rate so far is 10/17 patients (15 high-responders, 2 low-responders) or 59%, whereas in hemophilia B 6/9 patients (8 high-responders, 1 low-responder), or 67%, have become tolerant. In one hemophilia B patient, a relapse occurred after 6 months. During a second treatment episode he developed an acute myocardial infarction, probably caused by replacement with prothrombin complex concentrate. We conclude that the Malmö protocol is efficient for induction of immune tolerance but the patients must be selected particularly with regard to inhibitor duration and time of last booster.
Berntorp
E
E
Department for Coagulation Disorders, University of Lund, Malmö University Hospital, Sweden. erik.berntorp@medforsk.mas.lu.se
Astermark
J
J
Carlborg
E
E
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004338:Drug Combinations; D005164:Factor IX / Q000008:administration & dosage* / Q000276:immunology; D005167:Factor VII / Q000008:administration & dosage*; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology; D005500:Follow-Up Studies; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D002836:Hemophilia B / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000008:administration & dosage*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D008875:Middle Aged; D013548:Sweden
D004338:Drug Combinations; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D003520:Cyclophosphamide; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX