Lazarian Gregory, Cymbalista Florence, Baran-Marszak Fanny
Service d'Hématologie Biologique, Hôpital Avicenne, Assistance Publique des Hôpitaux de Paris, Paris, France.
Front Oncol. 2022 Feb 8;12:841630. doi: 10.3389/fonc.2022.841630. eCollection 2022.
In chronic lymphocytic leukemia (CLL), abnormalities are associated with reduced survival and resistance to chemoimmunotherapy (CIT). The recommended threshold to clinically report mutations is a matter of debate given that next-generation sequencing technologies can detect mutations with a limit of detection of approximately 1% with high confidence. However, the clinical impact of low-burden mutations with a variant allele frequency (VAF) of less than 10% remains unclear. Longitudinal analysis before and after fludarabine based on NGS sequencing demonstrated that low-burden mutations were present before the onset of treatment and expanded at relapse to become the predominant clone. Most studies evaluating the prognostic or predictive impact of low-burden mutations in untreated patients show that low-burden mutations have the same unfavorable prognostic impact as clonal defects. Moreover, studies designed to assess the predictive impact of low-burden mutations showed that mutations, irrespective of mutation burden, have an inferior impact on overall survival for CIT-treated patients. As low-burden and high-burden mutations have comparable clinical impacts, redefining the VAF threshold may have important implications for the clinical management of CLL.
在慢性淋巴细胞白血病（CLL）中，异常与生存率降低及对化学免疫疗法（CIT）的耐药性相关。鉴于下一代测序技术能够以高置信度检测到低至约1%的突变，临床上报告突变的推荐阈值存在争议。然而，变异等位基因频率（VAF）低于10%的低负荷突变的临床影响仍不明确。基于NGS测序对氟达拉滨治疗前后进行的纵向分析表明，低负荷突变在治疗开始前就已存在，并在复发时扩增成为主要克隆。大多数评估未治疗患者中低负荷突变的预后或预测影响的研究表明，低负荷突变与克隆缺陷具有相同的不良预后影响。此外，旨在评估低负荷突变的预测影响的研究表明，无论突变负荷如何，突变对接受CIT治疗的患者的总生存期的影响都较差。由于低负荷和高负荷突变具有相当的临床影响，重新定义VAF阈值可能对CLL的临床管理具有重要意义。
