Inhibition of Stem Cell Mobilization in Breast Cancer Patients by a Circulating Factor
Abstract
Preliminary data indicated some breast cancer patients who are candidates for high dose therapy requiring prior collection of a cytokine-mobilized blood stem cell harvest for reinfusion to restore hematopoiesis, respond poorly to mobilization. This makes collection of an adequate harvest inconvenient, prolonged and costly. Poor mobilizers appear to have a circulating inhibitor of mobilization which can be assayed in a mouse model. When injected before cytokine administration mobilization is significantly decreased. The goal of this project was to provide proof of principle of this hypothesis by assaying heparanized plasma from poorly mobilizing breast cancer patients as compared to good mobilizers (patients and normal donors) and begin to attempt to identify this inhibitor. Samples from 54 patients have been collected for assay. Initial studies indicated that mobilization of blood stem cells is more complex than previously appreciated and their may be early (days 1-2) and later (days 4-5) mobilization, the former differentially forming more differentiated progeniter cells (CFG-HPP and GM) and the latter more primitive (CD34+) stem cells. The mechanisms may be different. The assay has been refined to provide a more comprehensive evaluation of these possibilities before evaluating the remaining clinical samples. Employing serum amyloid A as a surrogate of IL-1 IL6 and TNFalpha activity eliminates these as candidates for the inhibitor. Potentially inhibition of early mobilization involves a chemokine inhibitor which will be evaluated next along with the remaining clinical samples.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1998
- Accession Number
- ADA359216
Entities
People
- John G. Sharp
Organizations
- University of Nebraska Omaha