瘤突变负载是高数单克隆B细胞淋巴细胞症患者治疗进展的预后
Geffen Kleinstern1,2, Nicholas J Boddicker2, Daniel R O'Brien2
1School of Public Health, University of Haifa, Haifa, Israel.
Blood advances
|February 15, 2024
概括
在高数单克隆B细胞淋巴细胞症 (HCMBL) 中的体性突变预测了慢性淋巴细胞白血病 (CLL) 的进展. 具有突变基因的HCMBL患者的治疗时间显著缩短,独立于CLL-IPI风险.
科学领域:
- 血液学 血液学 血液学
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
背景情况:
- 高计数单克隆B细胞淋巴细胞症 (HCMBL) 是慢性淋巴细胞白血病 (CLL) 的公认前体.
- 在CLL-国际预后指数 (CLL-IPI) 是预后时间到第一次治疗 (TTFT) 在HCMBL.
- 在HCMBL体质突变的预后意义仍然在很大程度上未被描述.
研究的目的:
- 为了研究体质突变基因在HCMBL中的预后影响.
- 为了比较HCMBL和未经治疗的CLL之间的突变频率.
- 评估突变基因和CLL-IPI对HCMBL中TTFT的综合预后价值.
主要方法:
- 在CLL中针对59个反复突变基因进行了针对性测序,对371名HCMBL个体的DNA进行了测序.
- 测序结果与855名以前未接受过治疗的CLL患者的队列进行了比较.
- 考克斯回归分析被用来估计TTFT的危险比率.
主要成果:
- 身体基因突变频率在HCMBL中较低 (52%),而不是CLL (70%).
- 与没有突变的患者相比,具有任何突变基因的HCMBL患者的TTFT短5.4倍,独立于CLL-IPI.
- 对突变基因和CLL-IPI的综合评估确定了HCMBL个体具有更具侵略性的临床过程,包括高风险患者的5年进展率为32%,低风险CLL的21%.
结论:
- 在诊断时,体基因突变在HCMBL中比在CLL中更少.
- 在HCMBL中存在突变基因是治疗时间缩短的重要独立预测因素.
- 将突变基因状态与CLL-IPI整合起来,可以提高HCMBL患者的风险分层,识别出具有更具侵略性的疾病轨迹的患者.
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