Elevated transforming growth factor beta levels in the plasma of cytokine-treated cancer patients and normal allogeneic stem cell donors.
BACKGROUND
Allogeneic blood stem-cell donors demonstrate more vigorous mobilization of CD34(+) cells to the circulation in response to cytokine administration than do autologous donors. Transforming growth factor (TGF-beta1) has been implicated as a mobilization inhibitor. A study was designed to determine whether plasma TGF-beta1 levels are elevated in cytokine-mobilized autologous cancer donors compared with cytokine-mobilized normal donors.


METHODS
Plasma collected from 29 autologous cancer donors and 33 normal allogeneic stem-cell donors following administration of mobilizing cytokines just prior to the first collection was assayed for TGF-beta1 using a sandwich-type ELISA. Plasma from three volunteers not treated with cytokine was also analyzed. Comparisons were made using the Student's t test on log-transformed data.


RESULTS
Average TGF-beta1 levels in the plasma of cancer patients were significantly higher than in allogeneic stem-cell donors (4.4 ng/mL versus 7.2 ng/mL; p = 0.038). The allogeneic donors required fewer collections to harvest greater numbers of CD34(+) cells and colony-forming unit granulocyte-macrophage (CFU-GM) than autologous donors. Plasma from three untreated volunteers had mean TGF-beta1 levels of 0.36 ng/mL, with all three levels below the 25th percentile for allogeneic donors and the 5th percentile for cancer patients.


CONCLUSIONS
Cytokine administration was associated with increased plasma TGF-beta1 levels. The levels were higher in cancer patients being mobilized for stem-cell collection than in allogeneic blood stem-cell donors. These differences could underlie the increased number of apheresis procedures required to harvest autologous graft products from cancer patients.
McGuire
T R
TR
Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha 68198-6045, USA.
Kessinger
A
A
Hock
L
L
Sharp
J G
JG
D018952:Antigens, CD34 / Q000378:metabolism; D001782:Blood Donors; D001943:Breast Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy; D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy; D009369:Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000097:blood*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D016212:Transforming Growth Factor beta; D016179:Granulocyte Colony-Stimulating Factor