title: Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors.
abstract: 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 (< or =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 (< or =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.
authors: Division of Pediatric Haematology-Oncology, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey. aysegulu@hotmail.com
authors: A
authors: A
authors: Unuvar
authors: K
authors: K
authors: Kavakli
authors: B
authors: B
authors: Baytan
authors: E
authors: E
authors: Kazanci
authors: T
authors: T
authors: Sayli
authors: H
authors: H
authors: Oren
authors: T
authors: T
authors: Celkan
authors: T
authors: T
authors: Gursel
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007223:Infant; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D001323:Autoantibodies; D005169:Factor VIII