title: Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up.
abstract: We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti-tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m(2)) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34(+) selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.
authors.affiliation: Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. rburt@northwestern.edu
authors.forename: Richard K
authors.initials: RK
authors.lastname: Burt
authors.forename: Robert M
authors.initials: RM
authors.lastname: Craig
authors.forename: Francesca
authors.initials: F
authors.lastname: Milanetti
authors.forename: Kathleen
authors.initials: K
authors.lastname: Quigley
authors.forename: Paula
authors.initials: P
authors.lastname: Gozdziak
authors.forename: Jurate
authors.initials: J
authors.lastname: Bucha
authors.forename: Alessandro
authors.initials: A
authors.lastname: Testori
authors.forename: Amy
authors.initials: A
authors.lastname: Halverson
authors.forename: Larissa
authors.initials: L
authors.lastname: Verda
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: Borko
authors.initials: B
authors.lastname: Jovanovic
authors.forename: Yu
authors.initials: Y
authors.lastname: Oyama
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000628:therapy*; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011817:Rabbits; D012074:Remission Induction; D015996:Survival Rate; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D019653:Myeloablative Agonists; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab