Abstract：
The mutational status of the IGHV gene is routinely assessed in patients with chronic lymphocytic leukaemia (CLL), since it is both prognostic of clinical outcome and predictive of response to treatment. This study evaluates the IGHV mutational status, assessed in newly diagnosed CLL patients, as a stand-alone predictor of time to first treatment (TTFT). We analysed the data of 236 CLL patients, diagnosed at our centre between January 2004 and September 2020, with a minimum follow-up period of 3.0 years, Binet A-B and Rai 0-II stages. IGHV was unmutated in 38.1 % and mutated in 61.9 % of cases. The univariate analysis showed a statistically significant difference (p < 0.001) in TTFT based on unmutated (85.2 % at 14 years, 95 % CI = 63.3-94.5 %) or mutated (41.3 % at 14 years, 95 % CI = 29.5-51.8 %) and the need for treatment at 1, 3 and 5 years was of 20.0 % vs 4.1 % (p < 0.001), 42.7 % vs 11.4 % (p < 0.001) and 55.8 % vs 20.0 % (p < 0.001) in unmutated and mutated IGHV patients, respectively. Multivariate analysis confirmed that unmutated IGHV status negatively affects TTFT (p < 0.001), in addition to high-risk genomic aberration (p = 0.025), Rai stage I (p = 0.007) and II (p-value < 0.001). The difference in TTFT based on unmutated or mutated IGHV status remains statistically significant also when considering the subgroups by the genomic aberrations and Rai stages. Our findings suggest that, with the single analysis of the IGHV mutational status at CLL diagnosis, along with clinical and laboratory data, and without karyotype and TP53 data, clinicians will have prognostic and predictive indications for the first clinical treatment and appropriate follow-up of patients.
摘要：
在慢性淋巴细胞白血病（CLL）患者中常规评估IGHV基因的突变状态，因为它既是临床结果的预后，也是治疗反应的预测。本研究评估了IGHV突变状态，在新诊断的CLL患者中评估，作为首次治疗时间（TTFT）的独立预测指标。我们分析了236例CLL患者的数据，2004年1月至2020年9月在我们中心确诊，最低随访期为3.0年，BinetA-B和Rai0-II阶段。38.1%的病例IGHV未突变，61.9%的病例发生突变。单变量分析显示，基于未突变的TTFT的统计学差异（p<0.001）（14年为85.2％，95%CI=63.3-94.5%)或突变(14年为41.3%，95％CI=29.5-51.8％），1、3和5年的治疗需求分别为20.0％和4.1％（p<0.001），在未突变和突变的IGHV患者中，42.7％vs11.4％（p<0.001）和55.8％vs20.0％（p<0.001），分别。多变量分析证实，未突变的IGHV状态对TTFT有负面影响（p<0.001），除了高风险的基因组畸变（p=0.025），Rai阶段I(p=0.007)和II(p值<0.001)。当通过基因组畸变和Rai阶段来考虑亚组时,基于未突变或突变的IGHV状态的TTFT的差异也保持统计学显著。我们的研究结果表明,通过对CLL诊断时IGHV突变状态的单一分析，以及临床和实验室数据，没有核型和TP53数据，临床医生将对患者的首次临床治疗和适当随访有预后和预测指征。
