IMMUNE TOLERANCE INDUCTION IN HEMOPHILIACS WITH INHIBITOR TO FVIII - HIGH-DOSE OR LOW-DOSE PROGRAM

In 1993-94, 15 high responders were treated in our centre according to the Malmo protocol which was modified as follows: serial plasmapheres is was performed instead of extracorporeal adsorbtion to protein A for reducing inhibitor levels and, after the bolus dose to neutralize the inhibitor, factor VIII concentrate was administered by a continuous i nfusion. Thus, this regimen included continuous infusion of factor VII I(FVIII) for 1-4 weeks, iv cyclophosphamide for 2 days and orally for 8-10 days, and intravenous immunoglobulin (IVIG) from the fourth day f or 5 days. All patients had been qualified for the treatment when the antibody level was < 15 BU mL(-1). Tolerance was induced in 10 patient s (66.6% very good and good results). The treatment failed in five cas es in which, due to a high inhibitor level, it was not possible to mai ntain a measurable factor VIII:C concentration throughout the whole pe riod of infusion. We compared these results with results of our low-do se regimen: 25 IU FVIII kg(-1) b.w. twice a week (1985-89, 11 high res ponders). The modified Malmo Protocol is much shorter than the low-dos e programme and this is a method of first choice in patients undergoin g surgery in the near future.