title: Immune tolerance induction using a factor VIII/von Willebrand factor concentrate (BIOSTATE), with or without immunosuppression, in Australian paediatric severe haemophilia A patients with high titre inhibitors: a multicentre, retrospective study.
abstract: BACKGROUND
  It has been postulated that factor VIII (FVIII) products containing von Willebrand factor (VWF) may improve immune tolerance induction (ITI) success rate in patients with haemophilia A and poor prognostic factors.
  
  
  METHODS
  We conducted a retrospective cohort analysis of a FVIII/VWF concentrate (BIOSTATE) for ITI in paediatric patients with severe haemophilia A (SHA) and inhibitors, from January 2003 to December 2011 at 3 paediatric-only Haemophilia Treatment Centres in Australia. Response to ITI was assessed at or before 33 months and at completion of ITI. Fifteen male patients with SHA were included in the analysis.
  
  
  RESULTS
  BIOSTATE was used for primary ITI in 8 patients (2 years, range 1.1-11.5 years) and for salvage ITI in 7 patients (9.9 years, range 1.1-15.4). At the end of the observation period there were 11 patients who achieved a complete response with BIOSTATE after a median duration of 21 months (range 5-85 months); a partial response was achieved in 2 patients in whom ITI is ongoing. Therefore, the overall response rate was 86.6%. Two patients were deemed treatment failures: one due to non-compliance after 18 months of ITI and another in whom a partial response had not been achieved after 22 months of ITI.
  
  
  CONCLUSIONS
  BIOSTATE was well-tolerated and effective when used for primary or salvage ITI in this cohort of paediatric patients with SHA and a high-level inhibitor.
authors.affiliation: Royal Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Robertson
authors.affiliation: Royal Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Pauline
authors.initials: P
authors.lastname: Higgins
authors.affiliation: Princess Margaret Hospital, Perth, Western Australia, Australia.
authors.forename: Jamie
authors.initials: J
authors.lastname: Price
authors.affiliation: Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: Scott
authors.initials: S
authors.lastname: Dunkley
authors.affiliation: CSL Limited, Melbourne, Victoria, Australia.
authors.forename: Giulio
authors.initials: G
authors.lastname: Barrese
authors.affiliation: Children's Hospital at Westmead, Sydney, New South Wales, Australia. Electronic address: Julie.curtin@health.nsw.gov.au.
authors.forename: Julie
authors.initials: J
authors.lastname: Curtin
mesh_terms: D000293:Adolescent; D001315:Australia / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005169:Factor VIII / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D014841:von Willebrand Factor / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D004338:Drug Combinations; C509423:factor VIII, von Willebrand factor drug combination; D014841:von Willebrand Factor; D005169:Factor VIII
keywords: BIOSTATE; Factor VIII, von Willebrand factor; Haemophilia A; Immune tolerance induction; Paediatric