原发与继发胰腺弥漫大B细胞淋巴瘤的临床特征及预后分析

Clinical characteristics and prognosis of primary and secondary diffuse large B-cell lymphoma of the pancreas

目的研究原发与继发胰腺弥漫大B细胞淋巴瘤(DLBCL)患者的临床特征及预后。方法回顾性分析2003年4月至2020年6月就诊于上海交通大学医学院附属瑞金医院的胰腺DLBCL患者的临床资料,采用靶向测序(55个淋巴瘤相关基因)评估患者的基因突变情况,采用单因素和多因素Cox回归模型评估患者总生存(OS)和无进展生存(PFS)的影响因素。结果共纳入80例患者,其中原发胰腺DLBCL 12例,继发胰腺DLBCL 68例。与原发胰腺DLBCL相比,继发胰腺DLBCL患者结外受累数目较多(P<0.001)、国际预后指数(IPI)评分较高(P=0.013)。原发与继发胰腺DLBCL患者OS和PFS的差异均无统计学意义(P值分别为0.120和0.067)。多因素分析结果显示,IPI评分中高危/高危(P=0.025)和双表达(DE)(P=0.017)是影响胰腺DLBCL患者OS的独立不良预后因素;IPI评分中高危/高危(P=0.021)是影响胰腺DLBCL患者PFS的独立不良预后因素。29例患者的靶向测序结果显示,PIM1、SGK1、BTG2、FAS、MYC和MYD88在胰腺DLBCL患者中的突变率大于20%,其中PIM1突变(OS:P=0.006,PFS:P=0.032)和MYD88突变(OS:P=0.001,PFS:P=0.017)与继发胰腺DLBCL患者较差的OS和PFS相关。结论原发与继发胰腺DLBCL患者的生存无显著差异,IPI评分中高危/高危、DE是影响胰腺DLBCL患者预后的不良因素。PIM1、SGK1、BTG2、FAS、MYC和MYD88是胰腺DLBCL中常见的突变,且具有PIM1及MYD88突变的患者预后不佳。

Objective To analyze the clinical characteristics and prognosis of primary and secondary pancreatic diffuse large B-cell lymphoma(DLBCL).Methods Clinical data of patients with pancreatic DLBCL admitted at Shanghai Rui Jin Hospital affiliated with Shanghai Jiao Tong University School of Medicine from April 2003 to June 2020 were analyzed.Gene mutation profiles were evaluated by targeted sequencing(55 lymphoma-related genes).Univariate and multivariate Cox regression models were used to evaluate the prognostic factors of overall survival(OS)and progression-free survival(PFS).Results Overall,80 patients were included;12 patients had primary pancreatic DLBCL(PPDLBCL),and 68 patients had secondary pancreatic DLBCL(SPDLBCL).Compared with those with PPDLBCL,patients with SPDLBCL had a higher number of affected extranodal sites(P<0.001)and had higher IPI scores(P=0.013).There was no significant difference in the OS(P=0.120)and PFS(P=0.067)between the two groups.Multivariate analysis indicated that IPI intermediate-high/high risk(P=0.025)and double expressor(DE)(P=0.017)were independent adverse prognostic factors of OS in patients with pancreatic DLBCL.IPI intermediate-high/high risk(P=0.021)was an independent adverse prognostic factor of PFS in patients with pancreatic DLBCL.Targeted sequencing of 29 patients showed that the mutation frequency of PIM1,SGK1,BTG2,FAS,MYC,and MYD88 in patients with pancreatic DLBCL were all>20%.PIM1(P=0.006 for OS,P=0.032 for PFS)and MYD88(P=0.001 for OS,P=0.017 for PFS)mutations were associated with poor OS and PFS in patients with SPDLBCL.Conclusion There was no significant difference in the OS and PFS between patients with PPDLBCL and those with SPDLBCL.IPI intermediate-high/high risk and DE were adverse prognostic factors of pancreatic DLBCL.PIM1,SGK1,BTG2,FAS,MYC,and MYD88 were common mutations in pancreatic DLBCL.PIM1 and MYD88 mutations indicated worse prognosis.