PDF(Pubmed)
Abstract：
UNASSIGNED: High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.
摘要：
HCMBL是慢性淋巴细胞白血病（CLL）的前兆。我们已经表明，在HCMBL患者中，CLL-国际预后指数（CLL-IPI）是首次治疗时间（TTFT）的预后。关于HCMBL个体中体细胞突变基因的预后影响知之甚少。我们使用CLL中59个反复突变基因的靶向测序小组对来自371个HCMBL个体的DNA进行测序，以鉴定高影响突变。我们将测序结果与我们的未治疗CLL队列（N=855）进行了比较，并采用Cox回归来估计与TTFT关联的风险比和95％置信区间（CI）。与CLL相比，HCMBL中任何突变基因的频率均较低(70%对52%).十年后，有任何突变基因的HCMBL个体中有37％需要治疗，而没有突变的HCMBL个体中有10％需要治疗;这导致有任何突变基因的HCMBL与没有突变基因的HCMBL相比，TTFT缩短了5.4倍（95CI：2.6-11.0）。独立于CLL-IPI。当根据CLL-IPI考虑具有低进展风险的个体时，具有任何突变的HCMBL个体的TTFT(95CI:1.6-11.8)比没有突变的个体短4.3倍。最后,当考虑CLL-IPI和任何突变的基因状态时，我们观察到与低风险CLL患者相比，两种预后因素均为高风险的HCMBL个体预后较差(即，5年进展率为32%对21%，分别)。在HCMBL中，在诊断时体细胞突变基因的频率低于CLL。考虑到突变基因的数量和CLL-IPI可以鉴定具有更积极临床病程的HCMBL个体。
