Department of Hematology Laboratory, ICO-Hospital Germans Trias i Pujol, Josep Carreras Leukaemia Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain.
Department of Genomics, Institut Germans Trias i Pujol, Badalona, Spain.
Hematol Oncol. 2019 Dec;37(5):564-568. doi: 10.1002/hon.2674. Epub 2019 Oct 25.
Patients with follicular lymphoma (FL) refractory to front-line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high-risk FL. Twenty-five patients with FL refractory to front-line ICT and 10 non-refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three-year progression-free survival (PFS) and OS probabilities were 25% (95% CI, 13%-41%) and 53% (34%-69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0-3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non-refractory). In conclusion, in this study, patients with high-risk follicular lymphoma were genetically heterogeneous.
滤泡性淋巴瘤（FL）患者对一线免疫化疗（ICT）耐药的总体生存（OS）较差。基因突变分析可能比经典的危险因素更能在治疗前准确地识别出这些患者。本研究旨在描述高危 FL 患者队列中选定基因突变的流行率。纳入了 25 例对一线 ICT 耐药的 FL 患者和 10 例年龄、性别和 FLIPI 评分匹配的非耐药患者。我们对先前报道可能具有预后影响的 18 个基因（定制靶向测序面板）进行了测序，包括确定 m7FLIPI 风险所需的 7 个基因。35 例患者的中位年龄为 62 岁。FLIPI 和 FLIPI2 分别为 27 例（84%）和 14 例（48%）较高。3 年无进展生存（PFS）和 OS 概率分别为 25%（95%CI，13%-41%）和 53%（34%-69%）。在 35 例患者的 18 个基因中存在 73 个变异。每个患者的突变中位数为 1（四分位距，0-3）。最常见的突变基因是 CREBBP（35 例中有 11 例，31%）和 EP300（35 例中有 10 例，29%）。EP300 突变与对治疗的耐药性相关（25 例耐药患者中有 10 例，10 例非耐药患者中无 0 例）。总之，在这项研究中，高危滤泡性淋巴瘤患者具有遗传异质性。
