title: Remission of refractory Crohn's disease by high-dose cyclophosphamide and autologous peripheral blood stem cell transplantation.
abstract: BACKGROUND
  Despite advances in immunosuppressive therapy, up to 10% of patients with severe Crohn's disease (CD) remain refractory to conventional treatment. Limited evidence from pilot trials suggests that high-dose immunosuppression and autologous peripheral blood stem cell transplantation (autoPBSCT) may induce remission in these patients, but there is substantial controversy regarding the safety and efficacy of this approach.
  
  
  OBJECTIVE
  To address this issue, a monocentre phase I/II trial of autoPBSCT was performed in patients with refractory CD in our hospital.
  
  
  METHODS
  Here, we report on the outcome of 12 patients with refractory CD treated with autoPBSCT. Briefly, CD34(+) -selected PBSCs were harvested after mobilisation therapy with cyclophosphamide and granulocyte-colony stimulating factor. Later, immunoablative conditioning therapy with high-dose cyclophosphamide followed by autoPBSCT was applied and clinical and endoscopic responses were analysed after a mean follow-up of 3.1 years (range 0.5-10.3 years).
  
  
  RESULTS
  PBSC harvest following mobilisation chemotherapy was successful in 11/12 patients and resulted in a clinical and endoscopic improvement in 7/12 patients. Subsequent conditioning and autoPBSCT were performed in nine patients and were relatively well tolerated. Among those, five patients achieved a clinical and endoscopic remission within 6 months after autoPBSCT. However, relapses occurred in 7/9 patients during follow-up, but disease activity could be controlled by low-dose corticosteroids and conventional immunosuppressive therapy.
  
  
  CONCLUSIONS
  Immunoablation by cyclophosphamide and autologous peripheral blood stem cell transplantation is safe and effective to induce remission of refractory Crohn's disease, and should be further evaluated in randomised controlled trials.
authors.affiliation: Department of Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Freiburg University Hospital,  Freiburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hasselblatt
authors.forename: K
authors.initials: K
authors.lastname: Drognitz
authors.forename: K
authors.initials: K
authors.lastname: Potthoff
authors.forename: H
authors.initials: H
authors.lastname: Bertz
authors.forename: W
authors.initials: W
authors.lastname: Kruis
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: A
authors.initials: A
authors.lastname: Stallmach
authors.forename: A
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: J
authors.initials: J
authors.lastname: Finke
authors.forename: W
authors.initials: W
authors.lastname: Kreisel
mesh_terms: D000328:Adult; D003131:Combined Modality Therapy; D003424:Crohn Disease / Q000503:physiopathology / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide