title: Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease.
  
  
  OBJECTIVE
  To evaluate the effect of autologous HSCT on refractory Crohn disease.
  
  
  METHODS
  Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids.
  
  
  METHODS
  All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed.
  
  
  METHODS
  Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging.
  
  
  RESULTS
  Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .052). Eight (34.8%) vs 2 (9.1%) patients were adjudicated free of active disease on endoscopy and radiology at final assessment (difference, 25.7% [95% CI, 1.1% to 47.1%]; P = .054). There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls. One patient undergoing HSCT died.
  
  
  CONCLUSIONS
  Among adult patients with refractory Crohn disease not amenable to surgery who had impaired quality of life, HSCT, compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year and was associated with significant toxicity. These findings do not support the widespread use of HSCT for patients with refractory Crohn disease.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00297193.
authors.affiliation: Nottingham Digestive Diseases Centre, School of Clinical Sciences, Queens Medical Centre, Nottingham, United Kingdom.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hawkey
authors.affiliation: APHP, Hôpital Saint Louis, Department of Gastroenterology, INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Allez
authors.affiliation: Nottingham Digestive Diseases Centre, School of Clinical Sciences, Queens Medical Centre, Nottingham, United Kingdom.
authors.forename: Miranda M
authors.initials: MM
authors.lastname: Clark
authors.affiliation: European Group for Blood and Marrow Transplantation, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: James O
authors.initials: JO
authors.lastname: Lindsay
authors.affiliation: Gastroenterology Department, Hospital Clinic, CIBER-EHD, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ricart
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: Hematology Department, Hospital Clinic, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Gastro-intestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.affiliation: IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
authors.affiliation: Haematology School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, United Kingdom.
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.affiliation: Centre for Haemato-Oncology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.affiliation: Department of Haematology, Western General Hospital, Edinburgh, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Johnson
authors.affiliation: Biotherapies and Cell Therapy Unit, AP-HP Hôpital Saint-Louis, Paris 7 University, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Larghero
authors.affiliation: Haematology/Transplantation, AP-HP Hôpital Saint-Louis, Paris 7 University, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Thieblemont
authors.affiliation: IBD Unit, Department of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.affiliation: Department of Hematology, University hospitals Leuven, Gasthuisberg, Belgium University Hospital, Belgium.
authors.forename: Daan
authors.initials: D
authors.lastname: Dierickx
authors.affiliation: Divisione Ematologia e Trapianto di Midollo, IRCCS San Martino-IST, Genova, Italy.
authors.forename: Adalberto
authors.initials: A
authors.lastname: Ibatici
authors.affiliation: Department of Haematology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
authors.forename: Timothy
authors.initials: T
authors.lastname: Littlewood
authors.affiliation: Hematology-BMT Center, Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Onida
authors.affiliation: Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Schanz
authors.affiliation: Department of Gastroenterology University Hospital Gasthuisberg Herestraat, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Hepato-Gastroenterology, Hopital Huriez, Lille, France23Department of Gastroenterology, Icahn School of Medicine, New York, New York.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Departement of Hematology, Hôpital Claude-Huriez, Lille, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Jouet
authors.affiliation: EBMT Clinical Trials, European Group for Blood and Marrow Transplantation, London, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Clark
authors.affiliation: European Blood & Marrow Transplantation Group, Hematology Department, Careggi University Hospital, Florence, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Saccardi
authors.affiliation: Department of Rheumatology, University Hospital, Basel, Switzerland.
authors.forename: Alan
authors.initials: A
authors.lastname: Tyndall
authors.affiliation: Translational Gastroenterology Unit, Oxford University Hospital, Oxford, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Travis
authors.affiliation: Internal Medicine and Vascular Disease Unit AP-HP Hôpital Saint-Louis, Paris 7 University, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Farge
mesh_terms: D000328:Adult; D003424:Crohn Disease / Q000628:therapy*; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012074:Remission Induction; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous; D016896:Treatment Outcome