The effect of granulocyte colony stimulating factor on genotoxicity in allogeneic peripheral blood stem cell transplantation donors: a prospective case-control study.

Hasan Fatih Çakmaklı, Hafize Gökçe, Esma Söylemez, Pervin Topçuoğlu, Zeliha Kayaaltı, Dilber Talia İleri
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Abstract

Background: Every year, thousands of donors are exposed to granulocyte-colony stimulating factor (G-CSF) for stem cell mobilization in hematopoietic stem cell transplantations (HSCT). Previous studies about the genotoxicity of G-CSF were inconclusive. In this study, the genotoxic effects of G-CSF in peripheral blood stem cell (PBSC) donors were evaluated prospectively by using three different validated and reliable methods for the first time in the literature to the best of our knowledge.

Methods: Donors of PBSC transplantation (n=36), who received G-CSF were evaluated for genotoxicity by micronucleus test (MNT), nuclear division index (NDI), and comet assay (CA). Genotoxic effects are expected to cause an increase in MNT and CA values and decrease in NDI. Blood samples were collected at three timepoints (TP): before starting G-CSF (TP1), after G-CSF for five days (TP2), and one month after the last dose (TP3). Sixteen controls were included for baseline comparison of genotoxicity tests. CD34 cell counts and hemograms were also analyzed.

Results: MNT and CA parameters; comet and tail length, tail DNA%, and tail moment, showed no change in time whereas another CA parameter, Olive`s tail moment (OTM) was increased significantly at TP3 compared to both baseline and TP2 (p=0.002 and p=0.017, respectively). Nuclear division index decreased significantly at TP2 (p < 0.001), then increased above baseline at TP3 (p=0.004). Baseline comparison with controls showed higher MN frequency in donors without statistical significance (p=0.059). Whereas, CA results were significantly higher in controls. CD34 cell count showed moderate positive correlation with white blood cell count at TP2 (Pearson R=0.495, p=0.004).

Conclusions: Our results showed the genotoxic effect of G-CSF in healthy donors, in two of the three tests performed, short-term effect in NDI, and long-lasting effect in OTM. So, this study provides novel information for the debate about the genotoxicity of G-CSF and supports the need for further studies with a larger sample size and longer follow-up.

粒细胞集落刺激因子对异基因外周血干细胞移植供体遗传毒性的影响:一项前瞻性病例对照研究。
背景:在造血干细胞移植(HSCT)中,每年有数千名捐献者暴露于粒细胞集落刺激因子(G-CSF)用于干细胞动员。先前关于G-CSF基因毒性的研究尚无定论。在本研究中,据我们所知,G-CSF对外周血干细胞(PBSC)捐献者的遗传毒性作用在文献中首次采用三种不同的经验证和可靠的方法进行了前瞻性评估。方法:采用微核试验(MNT)、核分裂指数(NDI)和彗星试验(CA)对36例接受G-CSF的外周血单个核细胞移植供体的遗传毒性进行评估。基因毒性作用预计会导致MNT和CA值增加,NDI降低。在三个时间点(TP)采集血样:开始G-CSF前(TP1)、G-CSF五天后(TP2)和最后一次给药后一个月(TP3)。16个对照组被纳入基因毒性试验的基线比较。CD34细胞计数和血象也进行了分析。结果:MNT和CA参数;彗星和尾部长度、尾部DNA%和尾部力矩在时间上没有变化,而另一个CA参数Olive的尾部力矩(OTM)在TP3时与基线和TP2相比显著增加(分别为p=0.002和p=0.017)。核分裂指数在TP2时显著下降(p<0.001),然后在TP3时高于基线(p=0.004)。与对照组的基线比较显示,供体的MN频率更高,没有统计学意义(p=0.059)。而对照组的CA结果显著更高。CD34细胞计数与TP2时的白细胞计数呈中度正相关(Pearson R=0.495,p=0.004)。结论:我们的结果显示,在三项测试中的两项测试中,G-CSF对健康供体具有遗传毒性作用,对NDI具有短期作用,对OTM具有长期作用。因此,这项研究为关于G-CSF基因毒性的争论提供了新的信息,并支持需要更大的样本量和更长的随访时间进行进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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