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Abstract: Background: Although new therapeutic strategies have been developed to control Crohn''s disease, medical treatment for refractory cases is not able to prevent extensive and/or repeat surgery. Recently, several cases have been reported of successful remission induction in Crohn''s disease patients by means of hematopoietic stem cell transplantation (HSCT). Here we report our long-term (4 to 6years) outcome in three patients. Patients: Three patients (two male, one female) with active severe Crohn''s disease were planned to undergo autologous HSCT. All patients were intolerant or refractory to conventional therapies, including anti-TNFα antibodies. Patients either refused surgery or surgery was considered not to be a feasible alternative due to the extensive disease involvement of the small intestine. Methods: Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4g/m2, followed on day 4 by subcutaneous injections with G-CSF 5μg/kg twice daily until leukapheresis. CD34+ cells were isolated after leukapheresis by magnetic cell sorting. In two of the three patients a second round of stem cell mobilization using G-CSF only was required, either because of low yield or because of insufficient recovery after CD34 selection. Prior to transplantation, immune ablation was achieved using cyclophosphamide 50mg/kg/day (4days), antithymocyte globulin 30mg/kg/day (3days) and prednisolone 500mg (3days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed. Results: All three patients successfully completed stem cell mobilization, and two of them subsequently underwent conditioning and autologous HSCT with CD34+ cell selection. Treatment was well tolerated, with acceptable toxicity. Now, 5 and 6years post-transplantation, these patients are in remission under treatment. The third patient went into remission after mobilization and therefore she decided not to undergo conditioning and HSCT transplantation. After a successful pregnancy she relapsed two years later. Since then, she suffers from refractory Crohn''s disease for which we are now reconsidering conditioning and transplantation. Conclusion: Autologous HSCT appears to be safe and can be an alternative strategy for Crohn''s disease patients with severe and therapy resistant disease. [Copyright &y& Elsevier]