title: Immune tolerance induction therapy for patients with hemophilia A and FVIII inhibitors particularly using low-dose regimens.
abstract: BACKGROUND
  Inhibitory antibodies against infused clotting factor VIII concentrates (FVIII) developed in 20-30% of patients with hemophilia A. Bypass therapy may control the bleeds in patients with FVIII inhibitors, however, immune tolerance induction (ITI) therapy is the only proven modality for eradicating FVIII inhibitors. Since the cost of high-dose (200 IU/kg) ITI is extremely expansive, we conducted this study to identify whether low-dose ITI can be an alternative strategy besides high-dose ITI or bypass therapy.
  
  
  METHODS
  Patients with hemophilia A and FVIII inhibitors treated by ITI in Kaohsiung Medical University Hospital from January 2000 to January 2010 were enrolled. Regimens of ITI therapy included high-dose (100 IU/kg) and low-dose (30-50 IU/kg).
  
  
  RESULTS
  High-dose ITI therapy for two high responders (HRs) and low-dose ITI therapy for three HRs and all low responders (LRs) were performed. Complete tolerance was achieved in 2 HRs with high-dose regimen, and in one HR and 19 LRs with low-dose regimens. We administered low-dose ITI combined with immune suppressants treatment for one of the patient with extremely high FVIII inhibitor titers and the inhibitor level markedly declined and no spontaneous bleeding episode was noticed during the treatment period.
  
  
  CONCLUSIONS
  The outcome of ITI in our study was satisfactory without clinically significant complications. Low-dose ITI regimens can effectively treat patients with high responder inhibitors, including one patient with extremely high inhibitor levels over 700 BU. Low-dose ITI may be an alternative modality for FVIII inhibitors management, especially in countries with limited resources.
authors.affiliation: Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Pei-Chin
authors.initials: PC
authors.lastname: Lin
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Liao
authors.forename: Shih-Pien
authors.initials: SP
authors.lastname: Tsai
authors.forename: Tai-Tsung
authors.initials: TT
authors.lastname: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000191:economics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000037:antagonists & inhibitors* / Q000276:immunology*; D006467:Hemophilia A / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007223:Infant; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII