弥漫大B细胞淋巴瘤并发滤泡淋巴瘤患者临床特征、基因突变谱及预后分析  

Clinical features, gene mutation profile and prognosis analysis of diffuse large B-cell lymphoma complicated with follicular lymphoma

作　　者：包维莺[1,3] 许彭鹏[1] 施晴 张慕晨 沈容 赫洋[1] 裘惠玲 易红梅 董磊[2] 王黎[1] 程澍[1] 钱樱[1] 赵维莅[1] Bao Weiying;Xu Pengpeng;Shi Qing;Zhang Muchen;Shen Rong;He Yang;Qiu Huiling;Yi Hongmei;Dong Lei;Wang Li;Cheng Shu;Qian Ying;Zhao Weili(Department of Hematology,Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine,State Key Laboratory of Medical Genomics,Shanghai Institute of Hematology,Shanghai 200025,China;Department of Pathology,Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China;Department of Hematology,Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(Preparatory Stage),Shanghai 201699)

机构地区：[1]上海交通大学医学院附属瑞金医院血液科,医学基因组学国家重点实验室,上海血液学研究所,上海200025 [2]上海交通大学医学院附属瑞金医院病理科,上海200025 [3]上海交通大学医学院附属松江医院(筹)血液科,上海201699

出　　处：《白血病．淋巴瘤》2023年第2期92-96,共5页Journal of Leukemia & Lymphoma

摘　　要：目的 探讨初诊弥漫大B细胞淋巴瘤(DLBCL)并发滤泡淋巴瘤(FL)(DLBCL/FL)患者的临床病理特征、基因突变谱和预后影响因素。 方法 回顾性分析2018年2月至2021年11月上海交通大学医学院附属瑞金医院收治的50例DLBCL/FL患者的临床病理资料。采用靶向测序评估55个淋巴瘤相关基因的突变状态。总结患者临床特征,评估患者近期疗效;采用Kaplan-Meier法分析患者总生存(OS)和无进展生存(PFS);采用Cox比例风险模型评估OS和PFS的影响因素。 结果 50例DLBCL/FL患者中,男性23例(46%),国际预后指数(IPI)评分≥2分22例(44%),16例(32%)为双表达淋巴瘤(DEL),4例(8%)为双打击淋巴瘤(DHL)。一线治疗后患者的完全缓解(CR)率为68%(34/50),总有效率为78%(39/50)。中位随访23.3个月(5.1~50.9个月),2年OS率为82.1%,2年PFS率为67.1%,中位OS和PFS均未达到。靶向测序显示,KMT2D、MYD88、TP53、BTG2、DTX1、EZH2、CD70、CREBBP、DUSP2、HIST1H1C、HIST1H1E和PRDM1基因的突变频率均超过15%。多因素Cox回归分析显示,男性( HR =4.264,95% CI 1.144~15.896, P =0.031)和IPI评分≥2分( HR =6.800,95% CI 1.771-37.741, P =0.007)是初诊DLBCL/FL患者PFS的独立危险因素,TP53突变( HR =4.992,95% CI 1.027~24.258, P =0.046)是OS的独立危险因素。 结论 DLBCL/FL患者中男女比例接近,DHL患者较少。KMT2D、MYD88、TP53等多种基因的突变在DLBCL/FL患者中较为常见。DLBCL/FL患者整体治疗反应性较高,且预后较好。男性和IPI评分≥2分是DLBCL/FL患者PFS的独立危险因素,TP53突变是OS的独立危险因素。Objective To investigate the clinicopathologic characteristics,gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma(DLBCL)complicated with follicular lymphoma(FL)(DLBCL/FL).Methods The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed.Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes.The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients.Kaplan-Meier method was used to analyze the overall survival(OS)and progression-free survival(PFS)of patients.Cox regression risk models were used to assess the factors affecting the OS and PFS.Results Among 50 DLBCL/FL patients,23 cases(46%)were male,22 cases(44%)had an international prognosis index(IPI)score≥2 points,16 cases(32%)were double-expression lymphoma(DEL)and 4 cases(8%)were double-hit lymphoma(DHL).The complete response(CR)and overall response rates were 68%(34/50)and 78%(39/50),respectively after the first-line therapy.The median follow-up time was 23.3 months(5.1-50.9 months).The 2-year OS rate was 82.1%and 2-year PFS rate was 67.1%;and the median OS and PFS were not reached.Targeted sequencing results showed that the mutation frequencies of KMT2D,MYD88,TP53,BTG2,DTX1,EZH2,CD70,CREBBP,DUSP2,HIST1H1C,HIST1H1E and PRDM1 genes in this cohort were more than 15%.Multivariate Cox regression analysis showed that male(HR=4.264,95%CI 1.144-15.896,P=0.031)and IPI score≥2 points(HR=6.800,95%CI 1.771-37.741,P=0.007)were independent risk factors of PFS in newly diagnosed DLBCL/FL patients,and TP53 mutation(HR=4.992,95%CI 1.027-24.258,P=0.046)was an risk influencing factor of OS.Conclusions The proportion of male and female DLBCL/FL patients is similar,with a small proportion of DHL.Mutations of KMT2D,MYD88 and TP53 genes are commonly found in DLBCL/FL patients.Generally,DLBCL/

关 键 词：淋巴瘤 大B细胞 弥漫性 淋巴瘤 滤泡性 突变 预后 双打击淋巴瘤 

分 类 号：R733.1[医药卫生—肿瘤]