2003; baxter - Supplements - Haematologica

[New Aspects in Treatment of Hemophilia B Patients]review paperThe Malmö immune toleranceexperience in hemophilia Bhaematologica 2003; 88(suppl. n. 12):71-74http://www.haematologica.org/free/immunotolerance2001.pdfERIK BERNTORPDepartment of Coagulation Disorders, Malmö UniversityHospital, Malmö, SwedenHemophilia B is a rare disorder with a comparativelylow incidence of inhibitors. Therefore, the experienceof immune-tolerance induction in hemophiliaB is restricted. The Malmö protocol for immune-toleranceinduction entails prednisone, factor IX,cyclophosphamide and intravenous immunoglobulinand if the inhibitor titer is >10 Bethesda units at thestart of treatment, the titer is lowered by using extracorporealadsorption to protein A. Nine patients withhemophilia B, complicated by an inhibitor, havebeen treated using a total of 13 attempts. Tolerancewas achieved in six of the eight high-respondingpatients and one patient relapsed after six months.The mean dose of factor IX during the treatmentepisodes was 182,000 units and the mean durationof treatment (success) was 25 days. The Malmö protocolgives a high response rate in the treatment ofhigh-responding factor IX inhibitor patients and, giventhe short treatment time, could be an option inorder to reduce treatment complications such asdevelopment of a nephrotic syndrome.Key words: haemophilia B, inhibitor, factor IX, immunetolerance inductionCorrespondence: Erik Berntorp, Department of CoagulationDisorders, Malmö University Hospital, SE-205 02 Malmö,Sweden. Phone: international +46.40.332392. Fax : international+46.40.336255.E-mail: erik.berntorp@medforsk.mas.lu.se.Hemophilia B is a rare disorder comparedto hemophilia A and the incidence ofinhibitors is less: 0-3.8% in hemophiliaB 1-4 compared to about 30% in hemophilia A. 5-7Inhibitors in severe hemophilia B are often associatedwith anaphylaxis or severe allergic manifestationson exposure to factor IX-containingproducts. 8 These complications jeopardize thepossibility of applying immune tolerance inductionin hemophilia B. Immune tolerance induction(ITI) has not been studied in as much detailin hemophilia B as it has been in hemophilia A.The reason for this is that the number ofinhibitor patients with haemophilia B is smaller9 and their treatment has been hampered bythe risk of thromboembolic complications withprothrombin complex concentrates given inhigh doses. The advent of purified factor IX concentratesin recent years has probably abolishedthis risk.Recent experience from immune toleranceinduction in hemophilia B has shown that thereis a risk of nephrotic syndrome developing inpatients who have had allergic reactions toinfused factor IX in close association with thedevelopment of an inhibitor to factor IX. 10Success has been reported with the Malmöprotocol in six of seven patients with highresponding inhibitors to factor IX. 11-13A modified Malmö protocol using continuousinfusion of factor IX with a dose of about300 IU/kg body weight daily for three weeks hasalso been tried in two patients without success. 14Today there is less agreement on how to treathemophilia B inhibitor patients than on how totreat hemophilia A ones, but the use of theMalmö regimen is one option as the course oftreatment is short, which should minimize therisk of development of nephrotic syndrome. Inthis report, an update is given of the experiencein Malmö using the Malmö protocol forimmune tolerance induction in hemophilia B.haematologica vol. 88(supplement n. 12):september 2003