2003; baxter - Supplements - Haematologica

IV International Workshop on Immune Tolerance in Hemophilia73Table 2. Malmö Treatment Model. Treatment and results ofITI in patients with severe hemophilia B.Patient No. of ITI Protein A ads Time inhibitor Toleranceattempts included detection to first ITI (y) achieved1 1 Yes 2 Yes2 2 Last ITI 9 Yes, relapseafter 6 months3 1 Yes 24 Yes4 1 Yes 10 Yes5 1 No 46 Yes6 1 No 22 Yes7 3 First ITI 2 No8 2 Last ITI 2 No9 1 No 26 NoTable 3. Malmö Treatment Model. Follow-up of patients withsevere hemophilia B (31 Dec., 2002).PatientFollow-up time (years)1 112 Relapse after 6 months3 19.54 175 Not known6 12.57 Not tolerant8 Not tolerant9 Not tolerantvated prothrombin complex concentrates shouldgive a booster effect in factor IX-deficientpatients. The definition of a tolerant state is asfollows: no measurable inhibitor, normal recoveryand half-life, and efficient prophylaxis withstandard doses, i.e. 25-40 IU/kg body weighttwice a week in hemophilia B. If tolerance isachieved and considered successful, the patientcontinues on ordinary prophylaxis. If tolerance isnot successful, the treatment can be repeatedafter 6-12 months when the inhibitor productionhas leveled out and reached a steady-state.A new attempt at a shorter interval will considerablyjeopardize the possibility of reducing theinhibitor by extracorporeal protein A adsorption,increase the cost of the treatment and probablydecrease the possibility of success.Concentrates usedProthrombin complex concentrate was used infive patients (Preconativ ® , Kabi; Prothromplex ® ,Immuno). Purified factor IX was used in fourpatients (Nanotiv ® , Pharmacia; Mononine ® ,Aventis Behring; Immunine ® , Baxter and Alphanine® , Alpha).ResultsNine patients were treated according to theMalmö protocol using a total of 13 attempts. Insix of the patients only one attempt was made.Protein A adsorption was used in six attempts.Tolerance was achieved in six of the eight highrespondingpatients. One patient relapsed aftersix months. This patient was treated again witha full treatment schedule including protein Aadsorption. A prothrombin complex concentratewas used. Two weeks after the start of treatmentthe patient developed an acute myocardial infarctionand died from heart failure two years later.Other events associated with the ITI includeheadache and one patient also experienced arterialbleeding in connection with puncture of theradial artery and developed a compartment syndrome.The patient recovered. The patients’ follow-upis indicated in Table 3. Thus, four patientshave been in a tolerant state for 10-20 years now.The treatment during the six successful ITIepisodes reveals that the total dose of factor IXused was (mean and range) 182,000 IU (92,000-430,000). The duration of treatment was 25 days(15-39) and the daily dose per kg body weight170 IU (91-291).DiscussionIn Malmö, we have treated nine patients withsevere hemophilia B complicated by inhibitors ofwhom eight had a high-responding inhibitor.Tolerance was achieved in six patients after onetreatment attempt. In three patients (one ofwhom had a low-responding inhibitor), thetreatment failed using six treatment episodes. Inone of the successful patients, a relapse was seenafter six months. Thus, the Malmö ITI-modelgives a high response rate in the treatment ofhigh-responding factor IX inhibitor (6/8patients), although one relapse was seen. Thesefigures do not include two patients who wereunsuccessfully treated with a modified protocol. 14No serious complications were seen due to theproduct treatment during the treatment episodes,in those cases in which purified factor IX concentrateswere used and none of the patientsdeveloped the nephrotic syndrome. One patientreported previous allergic reactions. This patient,who did not respond to the protocol, was treatedlater on with a high-dose, long-term factor IXregimen and developed proteinuria. Althoughaware that our case series is small, we would liketo draw the following tentative conclusion. TheMalmö ITI-model gives a high-response rate inthe treatment of high-responding factor IXinhibitor patients. Only purified factor IX concentratesshould be used in order to avoid thromboemboliccomplications and the short treatmenttime (mean: 25 days) minimizes the risk ofdeveloping a nephrotic syndrome using theMalmö protocol. The Malmö model for ITI inhemophilia B may be considered as a startingpoint for a larger prospective study to evaluateand compare cost-effectiveness and the rate ofhaematologica vol. 88(supplement n. 12):september 2003