Autologous hematopoietic stem cell transplantation in patients with refractory Crohn's disease.
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.
Oyama
Yu
Y
Division of Immunotherapy, Department of Medicine, Northwestern University Medical Center, Chicago, Illinois 60611, USA. y-oyama@northwestern.edu
Craig
Robert M
RM
Traynor
Ann E
AE
Quigley
Kathleen
K
Statkute
Laisvyde
L
Halverson
Amy
A
Brush
Mary
M
Verda
Larissa
L
Kowalska
Barbara
B
Krosnjar
Nela
N
Kletzel
Morris
M
Whitington
Peter F
PF
Burt
Richard K
RK
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