Lay Summary
Proposal No. IBD-0155
Principal Investigator: Christopher J. Hawkey, DM
Applicant Organization: University of Nottingham (United Kingdom)
Project Title: Autologous stem cell transplantation: international Crohn’s syndrome (ASTICS) trial
Period of Award: March 1, 2006 – February 29, 2013
Severe Crohn’s disease can have a major lifelong impact on health and quality of life. In general terms, Crohn’s disease develops when genetically susceptible white blood cells become inappropriately overactive causing inflammation in the bowel. Stem cell transplantation is a technique in which the inappropriately overactive white blood cells are eliminated from the body and replaced by undifferentiated stem cells.
The first step in the procedure is to harvest and save the patient’s own stem cells. This is done by suppressing the white cells with a drug called cyclophosphamide and then stimulating the bone marrow to release a large number of stem cells into the circulation where they can be collected for storage. About one month later, patients undergo immunoablation. This means that a very high dose of cyclophosphamide is used to kill off all the patient’s circulating white cells that give rise to inflammation in Crohn’s disease. The stored stem cells are then transfused into the patient where they develop into blood cells, including white cells.
This process of stem cell replacement and transplantation has been successful in a number of conditions in which blood cells are overactive. This has led some to try it out in Crohn’s disease and some reports are very impressive indeed and might amount to a cure. However, the process of stem cell transplantation is dangerous. Moreover, improvement in Crohn’s disease can sometimes occur spontaneously. Given that there is a great deal to gain if stem cell transplantation is an effective treatment and a lot to lose for individual patients as a result of severe side effects if it is ineffective, we consider it critical to evaluate the approach in a controlled way.
We propose to do this by conducting a trial in which patients suffering from severe Crohn’s disease will undergo stem cell transplantation, but be randomly allocated to have the procedure immediately or for it to be delayed by one year. By assessing symptoms, clinical course, blood tests and objective assessments of disease in the bowel over the first year, we will be able to say whether stem cell transplantation offers a benefit compared to control treatment without stem cell transplantation.
It is possible that the process of mobilization may give temporary benefit. All patients will undergo mobilization at baseline. The study has been structured to detect an improvement in the disease status of patients following mobilization with and without stem cell transplantation.