Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors

Summary.  The development of an inhibitor against factor VIII (FVIII) is a serious complication in children with haemophilia A. Immune tolerance induction (ITI) therapy is generally considered to be the best approach to eradicate the inhibitor. In this paper, the low-dose (≤50 IU kg^?1 twice or three times weekly with plasma-derived factor concentrates) ITI regimen used in Turkey is discussed. This regimen was given to 21 haemophilia A patients with high titer inhibitors. The median age at the beginning of ITI was 9 years and exposure days were 25. The median pre-ITI historical peak inhibitor titer, and inhibitor titer when ITI started were 80 BU (range 6.0–517), 19.2 BU (range 3.6–515), respectively. Complete immune tolerance was defined as the time at which at least two negative inhibitor assays was obtained with no anamnestic response. Our two cases were not reached in follow-up period. Immune tolerance could be achieved in 5 of 19 (26.3%) patients within a median time of 6 months. Partial tolerance was obtained in 7 patients while treatment failed in spite of significant decreased inhibitor levels in the other patients. A relapse developed in one immune-tolerized patient, one year later. The level of inhibitor titer at the beginning of ITI (≤10 BU), the pre-ITI historical peak inhibitor titer (<50 BU), and the time between the first diagnosis inhibitor to starting ITI (<12 months) were main factors in the success (complete or partial tolerance) of ITI. In conclusion, the outcome of low-dose ITI protocol was not satisfactory in this retrospective study.