Lay Summary

Proposal No.  IBD-0004
Principal Investigator:  Robert M. Craig, M.D.
Applicant Organization: Northwestern University (Chicago, Illinois, U.S.A.)
Project Title:  Immune ablation and hematopoietic peripheral stem cell support in patients with severe Crohn's disease
Period of Award:  March 1, 2002 - February 29, 2004

Crohn's disease (CD) is due to white blood cells (lymphocytes) that inappropriately attack an individual's own bowel.  Normally white cells only react against foreign material or pathogenic bacteria, but in CD, this process goes amiss.  Treatment of CD has mostly been:  1) directed at opposing inflammation with aspirin-like medicines or other anti-inflammatory drugs like steroids; 2) using antibiotics to influence the bowel bacteria; or 3) administering agents that suppress the actions of these white cells (azathioprine, 6-mercaptopurine), or the chemicals (cytokines) released by these cells (infliximab).  Some patients do poorly on these conventional medications and require surgery to remove the involved segments.  However, surgery does not cure the disease, as the disease usually returns.  In addition, surgery leaves the patient with less functional bowel, which may eventuate in the patient having insufficient bowel for nutrient absorption.

We propose to collect stem cells from the blood of patients with severe CD who have failed conventional therapy, and re-administer the same stem cells after the patients undergo chemotherapy that eliminates the patients' bone marrow and offending white blood cells.  The chemotherapy is the same as is used for bone marrow transplantation for leukemia or for cancer, and carries the risk of infection and bleeding during the time before the stem cells repopulate the bone marrow and allow for recovery (about 10 days).  The patients will be followed thereafter with x-rays of their bowel, colonoscopic examinations, blood tests, and physical examinations to determine if the treatment cures the CD.

Our initial studies in two patients were successful in ameliorating CD.  We need to study more patients and need to determine how long is the remission after stem cell transplantation.