Autologous hematopoetic stem cell transplantation for refractory Crohn disease a randomized clinical trial

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 treatment (controls). There were no statistically significant between-group differences in proportions of patients achieving sustained disease remission, CDAI less than 150 in the last 3 months, or freedom from active disease; there was a statistically significant difference among patients able to discontinue active treatment in the last 3 months. There were 76 serious adverse events in patients undergoing HSCT vs 38 in controls; 1 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