title: Immune tolerance induction in the treatment of paediatric haemophilia A patients with factor VIII inhibitors.
abstract: The development of an inhibitor to transfused factor VIII (FVIII) is a serious treatment-related problem in haemophiliac children. The management of patients 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 was attempted in 14 children with severe haemophilia A (13 high responders, one low responder), with daily doses of FVIII alone. FVIII dosage was chosen 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; during 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 half-life study. In the third (maintenance) phase, the children received either prophylactic therapy or episodic therapy for 12 months. The inhibitor elimination was defined as the time taken to achieve a negative inhibitor assay with no anamnestic response and normal FVIII recovery and/or normal half-life. Immune tolerance was achieved in 11 of 14 patients (79%) patients within a median time of 6 months; two children are still on therapy, three failed 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 low dose ITI regimen is not different from that reported by other investigators and the inhibitor elimination time is similar to some of the studies reported previously.
authors.affiliation: Children's Hospital of Michigan, Division of Haematology/Oncology, Detroit, MI 48201-2196, USA.
authors.forename: A
authors.initials: A
authors.lastname: Unuvar
authors.forename: I
authors.initials: I
authors.lastname: Warrier
authors.forename: J M
authors.initials: JM
authors.lastname: Lusher
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005169:Factor VIII / Q000008:administration & dosage / Q000276:immunology*; D005192:Family Health; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007223:Infant; D007518:Isoantibodies / Q000097:blood* / Q000627:therapeutic use; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012307:Risk Factors
chemical_list: D007518:Isoantibodies; D011994:Recombinant Proteins; D005169:Factor VIII