MedicalResearch.com Interview with:
Dr. Chris J. Hawkey, DM, FRCP, FMedSci.
University of Nottingham and Nottingham University Hospital
Medical Research: What is the background for this study?
Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn’s Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself. The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22).
ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint.
Medical Research: What are the main findings?
Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052).
But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died.
Medical Research: What should clinicians and patients take away from your report?
Dr. Hawkey: In this group of the most resistant cases of Crohn’s disease, autologous haemopoietic stem cell transplantation was an effective treatment, but it is not a miracle cure that could be applied to anyone with Crohn’s disease because it only seems to work in a minority of patients and it is the treatment is challenging and hazardous.
Haematopoietic stem cell transplantation is probably the most effective treatment for Crohn’s disease but also the most toxic. It cannot be recommended for widespread use at the present time but may be a risk worth taking for a small number of patients that have run out of treatment options. The challenge now is to find ways to identify those most likely to benefit and those who will not.
Dr. Chris J. Hawkey (2015). Stem Cell Therapy May Be Most Effective, and Most Toxic, Treatment For Crohn’s Disease