title: Autologous stem cell transplantation in severe treatment-resistant Crohn's disease: long-term follow-up of UK patients treated on compassionate basis.
abstract: BACKGROUND
  Although autologous stem cell transplantation (ASCT) may achieve disease control in severe treatment-resistant Crohn's disease (CD), relapse is frequent, and there is little information regarding long-term outcomes in terms of response to subsequent treatments and complications of ASCT.
  
  
  METHODS
  Retrospective evaluation of UK patients treated on a compassionate basis from three UK tertiary centres.
  
  
  METHODS
  We summarize long-term outcomes of six previously unreported patients with severe treatment-resistant CD treated with ASCT according to international guidelines between 2003 and 2009. Median duration of CD before ASCT was 14 (7-22) years. Following stem cell mobilization, patients were treated with high-dose cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (7.5 mg/kg) followed by ASCT.
  
  
  RESULTS
  All patients tolerated ASCT with routine toxicities and no treatment-related mortality and are alive at 50-123 months post-ASCT. Clinical and endoscopic remissions of CD were confirmed at 3 months post-ASCT in five patients, although median time to next treatment for inflammatory disease was 10 months (range: 3-16 months). Subsequently, disease control was achieved with previously ineffective and newer treatments, with surgery performed predominantly for pre-existing fibrotic strictures. Two patients became independent of home total parenteral nutrition (TPN). Reported late complications of ASCT included hypothyroidism and ovarian failure.
  
  
  CONCLUSIONS
  Long-term follow-up supports the safety and feasibility of ASCT as a means of achieving short-term control of severe CD whilst potentially re-sensitizing the disease to medical therapy and reducing requirements for surgery and TPN. Given the inevitability of relapse, pre-emptive salvage and/or maintenance treatments post-ASCT should be the focus of future trials.
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK john.snowden@sth.nhs.uk.
authors.forename: J A
authors.initials: JA
authors.lastname: Snowden
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: A
authors.initials: A
authors.lastname: Ansari
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: S
authors.initials: S
authors.lastname: Sachchithanantham
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: N
authors.initials: N
authors.lastname: Thompson
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: A
authors.initials: A
authors.lastname: Lobo
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: J
authors.initials: J
authors.lastname: Sanderson
authors.affiliation: From the Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Department of Oncology, University of Sheffield, Department of Gastroenterology, East Surrey Hospitals NHS Trust, Redhill, RH1 5RH Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London SE1 9RT Department of Haematology, Newcastle University, Newcastle-Upon-Tyne, NE1 7RU Department of Gastroenterology, Freeman Hospital, Newcastle-Upon-Tyne, NE7 7DN Department of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF and Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 9RT UK.
authors.forename: M
authors.initials: M
authors.lastname: Kazmi
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000628:therapy*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004351:Drug Resistance; D005240:Feasibility Studies; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D019653:Myeloablative Agonists; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide