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Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial

Hawkey, Christopher J.; Allez, Matthieu; Clark, Miranda M.; Labopin, Myriam; Lindsay, James O.; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndal, Alan; Travis, Simon; Farge, Dominique


Christopher J. Hawkey

Matthieu Allez

Myriam Labopin

James O. Lindsay

Elena Ricart

Gerhard Rogler

Montserrat Rovira

Jack Satsangi

Silvio Danese

Nigel Russell

John Gribben

Peter Johnson

Jerome Larghero

Catherine Thieblemont

Sandro Ardizzone

Daan Dierickx

Adalberto Ibatici

Timothy Littlewood

Francesco Onida

Urs Schanz

Severine Vermeire

Jean-Frederic Colombel

Jean-Paul Jouet

Elizabeth Clark

Riccardo Saccardi

Alan Tyndal

Simon Travis

Dominique Farge


Importance: 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.

Design, Setting, and Participants: 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.

Interventions: 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.

Main Outcomes and Measures: Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) less than 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 and Relevance: 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.

Trial Registration Identifier:NCT00297193


Hawkey, C. J., Allez, M., Clark, M. M., Labopin, M., Lindsay, J. O., Ricart, E., …Farge, D. (2015). Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial. Journal of the American Medical Association, 314(23), 2524-2534.

Journal Article Type Article
Acceptance Date Nov 12, 2015
Publication Date Dec 15, 2015
Deposit Date Nov 23, 2017
Journal JAMA
Print ISSN 0098-7484
Electronic ISSN 1538-3598
Publisher American Medical Association
Peer Reviewed Peer Reviewed
Volume 314
Issue 23
Pages 2524-2534
Public URL
Publisher URL
PMID 26670970