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JAMA. 2015 Dec 15;314(23):2524-34. doi: 10.1001/jama.2015.16700.

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

Author information

1
Nottingham Digestive Diseases Centre, School of Clinical Sciences, Queens Medical Centre, Nottingham, United Kingdom.
2
APHP, Hôpital Saint Louis, Department of Gastroenterology, INSERM UMRS 1160, Paris Diderot, Sorbonne Paris-Cité University, Paris, France.
3
European Group for Blood and Marrow Transplantation, Paris, France.
4
Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
5
Gastroenterology Department, Hospital Clinic, CIBER-EHD, Barcelona, Spain.
6
Division of Gastroenterology and Hepatology, University Hospital, University of Zurich, Zurich, Switzerland.
7
Hematology Department, Hospital Clinic, Barcelona, Spain.
8
Gastro-intestinal Unit, Institute of Genetics and Molecular Medicine, Western General Hospital University of Edinburgh, Edinburgh, United Kingdom.
9
IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy.
10
Haematology School of Medicine, University of Nottingham, Nottingham City Hospital, Nottingham, United Kingdom.
11
Centre for Haemato-Oncology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
12
Department of Haematology, Western General Hospital, Edinburgh, United Kingdom.
13
Biotherapies and Cell Therapy Unit, AP-HP Hôpital Saint-Louis, Paris 7 University, France.
14
Haematology/Transplantation, AP-HP Hôpital Saint-Louis, Paris 7 University, Paris, France.
15
IBD Unit, Department of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy.
16
Department of Hematology, University hospitals Leuven, Gasthuisberg, Belgium University Hospital, Belgium.
17
Divisione Ematologia e Trapianto di Midollo, IRCCS San Martino-IST, Genova, Italy.
18
Department of Haematology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
19
Hematology-BMT Center, Fondazione IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
20
Division of Hematology, University Hospital Zurich, Zurich, Switzerland.
21
Department of Gastroenterology University Hospital Gasthuisberg Herestraat, Leuven, Belgium.
22
Department of Hepato-Gastroenterology, Hopital Huriez, Lille, France23Department of Gastroenterology, Icahn School of Medicine, New York, New York.
23
Departement of Hematology, Hôpital Claude-Huriez, Lille, France.
24
EBMT Clinical Trials, European Group for Blood and Marrow Transplantation, London, United Kingdom.
25
European Blood & Marrow Transplantation Group, Hematology Department, Careggi University Hospital, Florence, Italy.
26
Department of Rheumatology, University Hospital, Basel, Switzerland.
27
Translational Gastroenterology Unit, Oxford University Hospital, Oxford, United Kingdom.
28
Internal Medicine and Vascular Disease Unit AP-HP Hôpital Saint-Louis, Paris 7 University, France.

Abstract

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) <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:

clinicaltrials.gov Identifier: NCT00297193.

PMID:
26670970
DOI:
10.1001/jama.2015.16700
[Indexed for MEDLINE]

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