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Vol. 30, Suppl. 3, 2012
Issue release date: January 2013
Dig Dis 2012;30(suppl 3):134–139

Stem Cells as Treatment in Inflammatory Bowel Disease

Hawkey C.J.
Nottingham Digestive Diseases Centre, Nottingham, UK

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Background: The Autologous Stem Cell Transplantation International Crohn’s Disease (ASTIC) trial is a randomised controlled evaluation of the proposition that immunoablation and haemopoietic stem cell transplantation improves the course of Crohn’s disease. Recruitment of all 48 patients in the trial will be completed in early 2012 and the results to date are descriptively presented here. Methods: Patients with an impaired quality of life due to active Crohn’s disease, despite the administration of at least 3 immunosuppressive agents, all received mobilisation treatment (cyclophosphamide 4 g/m2 over 2 days followed by recombinant human granulocyte colony stimulating factor (filgrastim) 10 µg/kg daily before randomisation to immediate (after 1 month) or delayed (after 1 year) immunoablation and stem cell transplantation. The conditioning regime was cyclophosphamide 50 mg/kg/day for 4 days, anti-thymocyte globulin 2.5 mg/kg/day and methylprednisolone 1 mg/kg on days 3–5. The bone marrow was reconstituted by the infusion of an unselected graft of 3–8 × 106/kg CD34-positive stem cells. Results were compared 1 year after mobilisation alone or after transplantation. Results: Twelve months after stem cell transplantation (early or delayed) the Crohn’s Disease Activity Index (CDAI) fell from 324 (median, interquartile range 229–411) to 161 (85–257, n = 17) compared to 351 (287–443) to 272 (214–331) following mobilisation alone (n = 11). Six patients had a normal CDAI after transplantation versus 1 after mobilisation. C-reactive protein fell from 16.6 (6.7–32.0) to 6.5 (3.5–12.5) mg/l versus 14 (8.0–27.0) to 9.0 (2.0–23.4) mg/l following mobilisation alone. The Crohn’s Disease Endoscopic Index of Severity (CDEIS) (aggregate for upper and lower endoscopy) fell from 18 (10–25) to 5 (1–11) following transplantation versus 14 (12–16) to 9 (4–22) following mobilisation. Three patients achieved the goal of a normal CDAI, no drug therapy and normal upper and lower endoscopy 1 year after transplantation, but so did 1 patient following mobilisation alone. Serious adverse events were common (n = 100 to date) with 42 infective episodes requiring or prolonging hospitalisation, following both mobilisation and conditioning and transplantation. There were 7 episodes of viral (re)activation. Temporary flare of Crohn’s disease activity or a need for surgery occurred in 8 patients. Conclusions: Immunoablation and haemopoietic stem cell transplantation appear to be an effective treatment for some patients with Crohn’s disease, although full results will be required for a firm conclusion. The risks are significant, making it potentially suitable for only a limited number of patients. Data from the whole trial will be needed to judge whether mobilisation alone has any benefits.

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