Clinical-alimentary tractAutologous hematopoietic stem cell transplantation in patients with refractory Crohn’s disease
Section snippets
Study design
This is a pilot study designed to investigate the safety and efficacy of HSCT utilizing high-dose cyclophosphamide, equine antithymocyte globulin, and autologous T cell-depleted (CD34+ cell-enriched) HSCT in patients with chronic active CD refractory to conventional therapies including infliximab. Primary end points were treatment-related toxicity and engraftment. Secondary end points were an HSC mobilization and disease response.
Patient selection
Patients and/or parents read and signed an informed consent form
Patient demographics and pre-HSCT disease manifestations
Twelve white patients (6 female and 6 male patients) with a median age of 27 years (range, 15–38 years) were enrolled. Five patients had significant pre-HSCT complications from standard immunosuppressive therapies. Three patients had either anaphylaxis or an anaphylactoid reaction from infliximab, while 6-mercaptopurine caused pancreatitis in 1 patient and prolonged cytopenias due to bone marrow suppression in another patient. The median duration of disease was 10 years (range, 1.5–20 years).
Discussion
The etiology of CD is unknown. No intestinal self-antigen (initiating or spread epitope) that is pathogenic has been identified. On the other hand, several animal gene knockout models suggest that inflammatory bowel disease may be a result of immune dysregulation between Th1 and Th2 cytokines. Deficiency of multiple Th2 cytokines may cause colitis in animal models. Interleukin 10-deficient mice develop acute and chronic colitis. 22 Interleukin 2-deficient, 23 double mutant interleukin 2- and
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Supported by a grant from the Broad Foundation (Los Angeles, CA).