title: Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease.
abstract: OBJECTIVE
  Crohn's disease (CD) is an immunologically mediated inflammatory disease of the gastrointestinal tract. Due to a high morbidity and/or an increase in mortality in refractory cases, a new treatment approach is needed. In theory, maximum immune ablation by autologous hematopoietic stem cell transplantation (HSCT) can induce a remission.
  
  
  METHODS
  We conducted a phase 1 HSCT study in 12 patients with refractory CD. Candidates were younger than 60 years of age with a Crohn's Disease Activity Index (CDAI) of 250-400 despite conventional therapies including infliximab. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony-stimulating factor and CD34 + enriched. The immune ablative (conditioning) regimen consisted of 200 mg/kg cyclophosphamide and 90 mg/kg equine antithymocyte globulin.
  
  
  RESULTS
  The procedure was well tolerated with anticipated cytopenias, neutropenic fever, and disease-related fever, diarrhea, anorexia, nausea, and vomiting. The median days for neutrophil and platelet engraftment were 9.5 (range, 8-11) and 9 (range, 9-18), respectively. The initial median CDAI was 291 (range, 250-358). Symptoms and CDAI improved before hospital discharge, whereas radiographic and colonoscopy findings improved gradually over months to years following HSCT. Eleven of 12 patients entered a sustained remission defined by a CDAI < or =150. After a median follow-up of 18.5 months (range, 7-37 months), only one patient has developed a recurrence of active CD, which occurred 15 months after HSCT.
  
  
  CONCLUSIONS
  Autologous HSCT may be performed safely and has a marked salutary effect on CD activity. A randomized study will be needed to confirm the efficacy of this therapy.
authors.affiliation: Division of Immunotherapy, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois 60611, USA. y-oyama@northwestern.edu
authors.forename: Yu
authors.initials: Y
authors.lastname: Oyama
authors.forename: Robert M
authors.initials: RM
authors.lastname: Craig
authors.forename: Ann E
authors.initials: AE
authors.lastname: Traynor
authors.forename: Kathleen
authors.initials: K
authors.lastname: Quigley
authors.forename: Laisvyde
authors.initials: L
authors.lastname: Statkute
authors.forename: Amy
authors.initials: A
authors.lastname: Halverson
authors.forename: Mary
authors.initials: M
authors.lastname: Brush
authors.forename: Larissa
authors.initials: L
authors.lastname: Verda
authors.forename: Barbara
authors.initials: B
authors.lastname: Kowalska
authors.forename: Nela
authors.initials: N
authors.lastname: Krosnjar
authors.forename: Morris
authors.initials: M
authors.lastname: Kletzel
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.forename: Richard K
authors.initials: RK
authors.lastname: Burt
mesh_terms: D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D010865:Pilot Projects; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome