Immune tolerance induction in the treatment of paediatric haemophilia A patients with factor VIII inhibitors

The development of an inhibitor to transfused factor VIII (FVIII) is a seri ous treatment-related problem in haemophiliac children. The management of p atients with high titre FVIII inhibitors is difficult, and immune tolerance induction (ITI) is the only method available for the eradication of these inhibitors. The results of the ITI regimen used at the Children's Hospital of Michigan Haemophilia Treatment Center are described and discussed. ITI w as attempted in 14 children with severe haemophilia A (13 high responders, one low responder), with daily doses of FVIII alone. FVIII dosage was chose n according to the patient's historical peak inhibitor titre. ITI included three phases; induction phase, dose reduction phase and maintenance phase. During the first phase, the starting dose was 50 or 100 U kg(-1) d(-1); dur ing the second phase the FVIII dosage was reduced gradually to 25 U kg(-1) every other day according to the inhibitor titre, FVIII recovery and/or hal f-life study. In the third (maintenance) phase, the children received eithe r prophylactic therapy or episodic therapy for 12 months. The inhibitor eli mination was defined as the time taken to achieve a negative inhibitor assa y with no anamnestic response and normal FVIII recovery and/or normal half- life. Immune tolerance was achieved in II of 14 patients (79%) patients wit hin a median time of 6 months; two children are still on therapy, three fai led ITI. We observed either failure or prolongation of immune tolerance if the historical peak titre or the maximum titre during ITI was >200 BU. The success rate of our tow dose ITI regimen is not different from that reporte d by other investigators and the inhibitor elimination time is similar to s ome of the studies reported previously.