Effects of Granulocyte Colony Stimulating Factor (G-CSF) On Monosomy 7 Aneuploidy and T Cell Subsets in Healthy Donors.

Abstract 3147

Poster Board III-84

Recent reports of chromosomal and immunological abnormalities in healthy donors receiving granulocyte colony stimulating factor (G-CSF) have raised concerns among hematologists that this popular cytokine may promote genomic instability or alter immune surveillance (Pampilon D et al Transfusion 2008; 48(7):1495-501). We previously reported that G-CSF altered the Th1:Th2 ratio in healthy individuals following short-term administration (Blood 2000 Apr 1;95(7):2269-74), but reported no new karyotypic abnormities after in vitro culture of bone marrow mononuclear cells with pharmacological doses of G-CSF (Proc Natl Acad Sci 2006 Sep 26;103(39):14483-8). There is no systematic study of the long-term effects of administering granulocyte colony stimulating factor (G-CSF) to healthy individuals. We examined CD34 cells of 10 healthy stem cell donors after they had received 10 mcg/kg G-CSF for 4 days; fluorescent in situ hybridization (FISH) was the method employed to monitor chromosomal changes. We also studied 37 healthy granulocyte donors who received G-CSF (5ug/Kg x 1 day) and dexamethosone for up to 42 times (median= 15; range 6-42) using FISH to examine chromosomes 7 and 8 and flow cytometry to define their T cell subsets. FISH did not detect chromosomal abnormalities in the CD34 cells of 10 donors mobilized with G-CSF; neither could monosomy 7 cells be isolated after culturing cells in media with 400 ng/mL G-CSF (previously shown to support outgrowth of monosomy 7 cells) for two weeks. Furthermore, FISH did not detect aneuploidy in the 37 regular granulocyte donors. Evaluation of T cell subsets by flow cytometry demonstrated similar percentages of CD4+ T cells in 18 granulocyte donors as compared to 23 untreated controls (57.5% vs 56.5%). However, donors had increased numbers of CD4+TNFαa+ Th1 T cells and decreased CD4+IL-6+ Th2 T cells (4.2% vs 1.6%, P= 0.0003 and 11% vs. 35%, P=0.04 respectively), while the donor Th2 subset expressed significantly more IL-6 per cell (P<0.01). CD4+CD25+FoxP3+ regulatory T cells (Tregs) were significantly increased in G-CSF-treated donors (10.1% vs 6.0%, P<0.0001), while Th17 T cells were not significantly different (2.4% vs 0.7%, P=0.423). G-CSF does not produce chromosomal abnormalities of monosomy 7 or trisomy 8 in healthy SCT donors or in serially treated granulocyte donors. However, there are significant changes in T cell subsets that modulate the immune response.

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