title: Autologous T cell depleted haematopoietic stem cell transplantation in children with severe juvenile idiopathic arthritis in the UK (2000-2007).
abstract: As part of collaborative multi-centre study started in 2000, 7 children in the UK fulfilled the inclusion criteria for treatment with autologous T cell depleted (TCD) haematopoietic stem cell transplantation (HSCT) for severe juvenile idiopathic arthritis (JIA). Here we report on the outcome and transplant-related complications.
  
  
  RESULTS
  The initial, often dramatic clinical response in all patients was followed in 4 with sustained benefit, including the withdrawal of immunosuppressive and anti-inflammatory treatment, significant catch-up growth and immense improvement of the quality of life during 5-8 years long follow-up. Two patients relapsed within 1-12 months, and one died 4 months post transplant.
  
  
  RESULTS
  Adenovirus reactivation with dissemination was lethal in one patient, whilst Epstein-Barr (EBV) and cytomegalovirus (CMV) reactivation-driven haemophagocytic syndrome responded to antiviral and immunomodulatory treatment in 2 patients. Both the conditioning and the T cell depletion of the graft, leading to severe immunosuppression and prolonged immune system function reconstitution, are the main predisposing factors for potentially life-threatening transplant-related complications.
  
  
  CONCLUSIONS
  Autologous TCD HSCT for children with severe JIA results in two-phase response. The initial remission seen in all patients is due to immunosuppressive conditioning. This is followed by sustained drug-free remission in over 50% of patients, which is due to 'immunomodulatory' effects of TCD HSCT. The procedure carries a significant morbidity and mortality risk. However, this risk should be balanced against the risks of life-threatening infections occurring in this very selective group of patients on long-term and combined immunosuppressive and anti-inflammatory therapies. How to correctly identify and appropriately assess the patients in need for autologous TCD HSCT, particularly in relation to optimizing the timing for the procedure in regards to the newly available therapies with different biologic response modifiers, are some of the most important questions awaiting answers from this on-going study.
authors.affiliation: Department of Paediatric Immunology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. mario.abinun@ncl.ac.uk
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Flood
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cant
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.forename: Helen E
authors.initials: HE
authors.lastname: Foster
authors.forename: Mark
authors.initials: M
authors.lastname: Friswell
authors.forename: Eileen
authors.initials: E
authors.lastname: Baildam
authors.forename: Joyce
authors.initials: J
authors.lastname: Davidson
authors.forename: Taunton R
authors.initials: TR
authors.lastname: Southwood
authors.forename: Polly
authors.initials: P
authors.lastname: Livermore
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000150:complications / Q000401:mortality / Q000628:therapy*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D008212:Lymphocyte Depletion; D008297:Male; D018579:Patient Selection; D018570:Risk Assessment; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D006113:United Kingdom; D014775:Virus Activation