9. Clinical and endocopic improvement following hemopoietic stem cell transplantation in the ASTIC trial
C. Hawkey1, M. Allez2, S. Ardizzone3, M. Clark1, L. Clark4, J.-F. Colombel5, S. Danese6, D. Farge-Bancel7, M. Labopin8, J. Lindsay9, A. Norman1, F. Onida10, E. Ricart11, G. Rogler12, M. Rovira11, N. Russell13, J. Satsangi14, S. Travis15, A. Tyndall16, S. Vermeire17, 1University of Nottingham, Nottingham Digestive Diseases Centre, Nottingham, United Kingdom, 2Hôpital Saint-Louis, Paris, France, 3L. Sacco University Hospital, Milan, Italy, 4European Group for Blood and Marrow Transplantation, United Kingdom, 5Hôpital Huriez, Lille, France, 6Istituto Clinico Humanitas, Milan, Italy, 7Unité de Médecine Interne et Pathologie Vasculaire, France, 8European Group for Blood and Marrow Transplantation, France, 9Barts & the London School of Medicine, United Kingdom, 10University of Milan, Italy, 11Hospital Clinic Barcelona, Spain, 12University Hospital of Zürich, Switzerland, 13University of Nottingham, Clinical Haematology, Nottingham, United Kingdom, 14University of Edinburgh, United Kingdom, 15John Radcliffe Hospital, United Kingdom, 16University Hospital of Basel, Switzerland, 17University Hospitals Leuven, Belgium
The Autologous Stem Cell Transplantation International Crohn's Disease (ASTIC) Trial is a randomised controlled trial co-sponsored by ECCO and EBMT (Autoimmune Diseases) and supported by the Broad Foundation that investigates haemopoietic stem cell transplantation (HSCT) in Crohn's disease (CD). The primary endpoint is measured at one year and all but one patient will have reached this endpoint by February 2013.
Patients with impaired quality of life and active CD, despite >3 immunosuppressive agents all received mobilisation (iv cyclophosphamide 4gm/M2 followed by filgrastim 10 µ/kg/d before randomisation to immediate (1 month) or delayed (13 months) immunoablation and HSCT. Conditioning was with iv 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 before an unselected graft of 3–8×106/kg CD34+ stem cells was infused. Symptoms (Crohn's disease activity index, CDAI), endoscopy (Simple Endoscopic Score, SES) and quality of Life are compared 1 year after mobilisation alone or after HSCT. The trial tests whether HSCT can achieve sustained remission (defined as no immunosuppressive drugs and a CDAI <150 over 3 months before the 1 year assessment, with endoscopy/imaging showing no evidence of active CD).
As of Nov 2012, data are available on 30/45 patients. In 14 undergoing mobilisation and HSCT the CDAI fell by 162 (median, IQR 0–190), from 322 (253–386) to 161 (73–246). Following mobilisation alone (n = 16) the fall was 82 (41–137) from 351 (313–435) to 298 (220–370). The aggregate SES was 16.0 (10.0–25.0) before and 3.0 (1.8–12.0) after HSCT, a fall of 7.0 (7.0–14.0). For mobilisation alone, there was no change in the SES (IQR 5.0 rise to 12.0 fall) with a median score of 12.1 (6.5–14.0) before and 6.5 (3.0–10.3) at 1 year. There have been 62 SAEs in 19 patients randomised to early transplantation and 58 in 18 patients randomised to delayed transplantation. One patient died following HSCT. Results concerning all but one patient with 1 year primary assessment data by February 2013 will be presented.
Immunoablation and HSCT appears to be an effective treatment for patients with Crohn's Disease that may substantially reduce endoscopic evidence of disease, but carries a high chance of adverse events. Final results will allow a rational evaluation of the effectiveness and safety of HSCT.