Long-term follow-up of autologous hematopoietic stem cell transplantation for severe refractory Crohn's disease

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, the Netherlands.
Journal of Crohn s and Colitis (Impact Factor: 6.23). 12/2011; 5(6):543-9. DOI: 10.1016/j.crohns.2011.05.004
Source: PubMed


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 6 years) outcome in three 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.
Peripheral blood stem cells were mobilized using a single infusion of cyclophosphamide 4 g/m(2), followed on day 4 by subcutaneous injections with G-CSF 5 μg/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 (4 days), antithymocyte globulin 30 mg/kg/day (3 days) and prednisolone 500 mg (3 days). Endoscopy, barium small bowel enteroclysis and MRI enterography were performed.
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 6 years 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.
Autologous HSCT appears to be safe and can be an alternative strategy for Crohn's disease patients with severe and therapy resistant disease.

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    • "Moreover, a plenty of patients may present with deleterious side effects such as nausea, allergy, adrenal impairment and pancreatitis , as a consequence of the current therapies (Rutgeerts et al. 1990; Akobeng and Gardener 2005; Fidder et al. 2009). In view of that, in the last years novel treatment modalities have been tried in patients with severe refractory Crohn's disease and one the most successful approaches has been the use of high-dose immunosuppression protocols, usually involving cyclophosphamide, associated with autologous hematopoietic stem cells transplantation (Burt et al. 2003, 2010; Oyama et al. 2005; Hommes et al. 2011). On the other hand, total body irradiation (TBI) associated with chemotherapy is the first choice in the treatment of some hematological disorders such as follicular lymphoma (Richaud et al. 1998; Chow et al. 2010). "
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