TY - JOUR
T1 - Effects of granulocyte-colony stimulating factor on chromosome aneuploidy and replication asynchrony in healthy peripheral blood stem cell donors
AU - Hirsch, Betsy A
AU - Oseth, Le Ann
AU - Cain, Meghan
AU - Trader, Erin
AU - Pulkrabek, Shelley
AU - Lindgren, Bruce R
AU - Luo, Xianghua
AU - Clay, Mary
AU - Miller, John
AU - Confer, Dennis
AU - Weisdorf, Daniel J
AU - Mc Cullough, Jeffrey
PY - 2011/9/1
Y1 - 2011/9/1
N2 - As peripheral blood has surpassed bone marrow as a predominant source of stem cells for transplantation, use of the cytokine granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSCs) is increasing. Issues regarding potential genotoxic effects of even short-term, low-dose G-CSF treatment for the healthy donors have been raised. To address the question of chromosomal instability, we used FISH to evaluate the peripheral blood lymphocytes of 22 PBSC donors and 22 matched controls at 5 time points over a 12-month period. The specimens obtained were a pre-G-CSF, followed by collections at the time of PBSC harvest (days 5-7) and at 2, 6, and 12 months after donation. Eight additional PBSC donors provided a single sample at 12 months. Nine loci (mapped to chromosomes 7, 8, 9, 17, 21, and 22) were evaluated for aneuploidy, including 3 mapped to chromosome 7 because of the specific relevance of monosomy 7. Replication timing was evaluated for chromosome 15 and 17 loci. No evidence was found of G-CSF-induced chromosomal instability. This work supports the epidemiologic data that have demonstrated no increased risk for hematologic malignancies in G-CSF-primed PBSC donors.
AB - As peripheral blood has surpassed bone marrow as a predominant source of stem cells for transplantation, use of the cytokine granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSCs) is increasing. Issues regarding potential genotoxic effects of even short-term, low-dose G-CSF treatment for the healthy donors have been raised. To address the question of chromosomal instability, we used FISH to evaluate the peripheral blood lymphocytes of 22 PBSC donors and 22 matched controls at 5 time points over a 12-month period. The specimens obtained were a pre-G-CSF, followed by collections at the time of PBSC harvest (days 5-7) and at 2, 6, and 12 months after donation. Eight additional PBSC donors provided a single sample at 12 months. Nine loci (mapped to chromosomes 7, 8, 9, 17, 21, and 22) were evaluated for aneuploidy, including 3 mapped to chromosome 7 because of the specific relevance of monosomy 7. Replication timing was evaluated for chromosome 15 and 17 loci. No evidence was found of G-CSF-induced chromosomal instability. This work supports the epidemiologic data that have demonstrated no increased risk for hematologic malignancies in G-CSF-primed PBSC donors.
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U2 - 10.1182/blood-2011-04-348508
DO - 10.1182/blood-2011-04-348508
M3 - Article
C2 - 21719598
AN - SCOPUS:80052415559
SN - 0006-4971
VL - 118
SP - 2602
EP - 2608
JO - Blood
JF - Blood
IS - 9
ER -