2003; baxter - Supplements - Haematologica

84L. Hess et al.Table 3.ular intervals as specified in the MBM Protocol incombination with immunoadsorption and thecontinued endogenous FVIII synthesis resultedin detectable factor VIII plasma levels within thefirst 1-2 apheresis treatments.In addition, application of exogenous factorVIII creates an antigen stimulus, which ininhibitor patients both of acquired as well as congenitalgenesis results in a booster effect due toincreased lymphocyte proliferation. 27,28 Thisshould also be discussed with regard to an elevatedsensitivity of inhibitor clones towardsimmunosuppressants.A minor booster effect is also observed duringthe first treatment cycle of the MBM Protocol.This is of no clinical relevance in the presence ofdetectable FVIII recovery values. This short-termquantitative increase in inhibitor activity is neutralizedby the patient’s exogenous and endogenousFVIII levels as FVIII plasma activity remainsdetectable and there is clinical proof of a hemostaticeffect. In the end, booster effect is of lowclinical relevance as the inhibitor titers are nolonger detectable after a median of five apheresisdays. Whether or not booster effect is of any elementarysignificance for inhibitor eliminationcannot be decided at present. There is empiricalproof at least of limited effectiveness of prednisoloneand cyclophosphamide in the treatmentof hemophilia patients with alloantibodies asopposed to the treatment of patients withacquired autoantibodies. 25 In the combination ofmeasures (FVIII, immunoadsorption, IgG application)the additional immunosuppressive effectleads to permanent inhibitor elimination. TheFVIII levels measured, as in the case reported, are6-8-12-hour recovery values. We can assumethat after application of FVIII plasma levels arereached which sufficiently explain the earlyhemostatic effect we have observed, even at lowrecovery values. 24 Therapeutic response cantherefore be monitored by determination of FVIIIactivity, apart from the clinical parameters. Ourexperience suggests that the factor VIII activitiesmeasured by one-stage clotting assay are closelyrelated to bleeding tendency and its decrease duringthe MBM Protocol.This type of factor VIII determination allowsmonitoring the treatment of bleedings as well asthe success of therapy, so that treatment can beadjusted as appropriate. Comparable laboratorymonitoring is currently not available for APCC orrFVIIa therapy, or only at an unsatisfactory level.8,29The MBM Protocol consists of two components:the modified Bonn Protocol and the modifiedMalmö Protocol. In the Bonn Protocol, which wasdeveloped in 1974/75, 100-150 factor VIIIunits/kg BW are applied daily until permanentinhibitor elimination. For the Malmö Protocol,the Bonn Protocol was modified, and infusion ofcomparable amounts of factor VIII is preceded byimmunoadsorption if the inhibitor titer exceeds10 BU. As opposed to the Malmö Protocol theMBM Protocol involves long-term immunoadsorptionover several weeks. The target volume tobe absorbed within one apheresis day (2.5 timesthe plasma volume) is reached after 4-5 hours.This permits quick inhibitor reduction and, withthe Therasorb columns used, the binding of allIgG subclasses.In addition, immunosuppressive therapy waschanged from short-term bolus therapy usingcyclophosphamide within the Malmö Protocol tocontinuous oral administration in combinationwith oral prednisolone for up to 6 weeks afterinhibitor eradication.IgG is applied in a changed mode on a regularand standardized basis after several days ofimmunoadsorption.Conclusive assessment is problematic due tothe difficult data situation in current literature.haematologica vol. 88(supplement n. 12):september 2003