Introduction The Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) Trial is a randomised controlled evaluation of the proposition that immunoablation and hemopoietic stem cell transplantation improves the course of Crohn's disease. Recruitment of all 48 patients in the trial will complete in early 2012 and results to date are presented descriptively here.
Methods Patients with impaired quality of life due to active Crohn's disease, despite at least three immunosuppressive agents all receive mobilisation treatment (intravenous cyclophosphamide 4 gm/m2 over 2 days followed by recombinant human granulocyte-colony stimulating factor [GCSF, filgrastim], 10 μ/kg daily before randomisation to immediate (1 month) or delayed (1 year) immunoablation and stem cell transplantation. The conditioning regime is intravenous cyclophosphamide 50 mg/kg per day for 4 days, anti-thymocyte globulin 2.5 mg/kg/day and methyl prednisolone 1 mg/kg on days 3–5. The bone marrow is reconstituted by infusion of an unselected graft of 3–8×106/kg CD34 positive stem cells. Results are 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, IQR 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 vs one after mobilisation. C reactive protein fell from 16.6 (6.7–32.0) mg/l to 6.5 (3.5–12.5) mg/l vs 14 (8.0–27.0) mg/l 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 vs 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 tranplantation but so did one 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 seven episodes of viral (re)activation. Temporary flare of Crohn's disease activity or a need for surgery occurred in eight patients.
Conclusion Immunoablation and hemopoietic stem cell transplantation appears to be an effective treatment for some patients with Crohn's Disease, although full results will be required for a firm conclusion. 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.
Competing interests None declared.