166例双表达弥漫大B细胞淋巴瘤临床特征与预后分析

Clinical features and prognosis of 166 cases of MYC/BCL2 double-expression diffuse large B-cell lymphoma

目的探讨双表达弥漫大B细胞淋巴瘤(DLBCL)的临床特征与预后。方法回顾性分析2016年1月至2020年12月北京大学第三医院收治的166例双表达DLBCL患者的临床资料, 分析患者的临床特征、生存和预后因素。结果共收集DLBCL患者410例, 其中双表达淋巴瘤(DEL)166例(40.5%)。男82例, 女84例, 中位诊断年龄63.5(21~95)岁。110例(66.3%)患者初诊年龄≥60岁, 106例(106/163, 65.0%)患者诊断时LDH升高, 74例(74/160, 46.2%)诊断时β2-微球蛋白(β2-MG)≥ 3 mg/L, 107例(107/163, 65.6%)结外受累数目≥2个, 65例(65/166, 39.2%)有B症状, 131例(131/165, 79.4%)初诊时分期为Ⅲ、Ⅳ期, 41例(41/161, 25.5%)初诊时国际预后指数(IPI)评分0~2分, 38例(38/161, 23.6%)初诊时IPI评分3分, 82例(82/161, 50.9%)初诊IPI评分4~5分。DEL患者中9例(9/56, 16.1%)具有MYD88和CD79B突变。单因素分析显示, 年龄≥60岁(P=0.004)、β2-MG水平升高(P=0.002)、IPI评分高(P=0.003)与较差的总生存(OS)相关, β2-MG水平升高(P=0.031)、LDH水平升高(P=0.017)、分期Ⅲ~Ⅳ期(P=0.001)、IPI评分高(P=0.013)、免疫组化p53突变型(P=0.049)和PIM1突变(P=0.039)与较差的无进展生存(PFS)相关。多因素分析显示, IPI评分4~5分(HR=2.622, 95%CI 1.398~4.917, P=0.003)是影响DEL患者OS的独立危险因素。生存分析显示, DEL与非DEL患者的PFS率差异有统计学意义(65.6%对75.1%, P=0.002), 而OS率的差异无统计学意义(81.8%对83.6%, P=0.226)。在DEL患者中, REPOCH方案的总有效率高于RCHOP或RCHOP样方案(81.5%对63.4%, P=0.004)。结论 DEL是一组侵袭性较强的淋巴瘤, 具有较差的PFS, 采用REPOCH方案化疗可能会改善患者的整体预后。

Objective To investigate the clinical features and prognosis of MYC/BCL2 double-expression diffuse large B-cell lymphoma(DEL).Methods The clinical data,including clinical characteristics,survival,and prognostic factors,of 166 patients with DEL treated at Peking University Third Hospital from January 2016 to December 2020 were retrospectively analyzed.Results A total of 410 patients with diffuse large B-cell lymphoma were collected,including 166 cases(40.5%)of DEL.There were 82 males and 84 females with a median age of 63.5(21-95)years at diagnosis.A total of 110 patients(66.3%)were aged over 60 years at initial diagnosis,106 patients(106/163,65.0%)had elevated lactate dehydrogenase(LDH)at diagnosis,74 patients(74/160,46.2%)hadβ2 microglobulin level over 3 mg/L at diagnosis,and 107 patients(107/163,65.6%)had≥2 extranodal involvement.Sixty-five patients(65/166,39.2%)had B symptoms,131 patients(131/165,79.4%)had stageⅢandⅣdisease at initial diagnosis,41 patients(41/161,25.5%)had an International Prognostic Index(IPI)score of 0-2 at initial diagnosis,and 38 patients(38/161,23.6%)had an IPI score of 3 at initial diagnosis.Eighty-two patients(82/161,50.9%)had an IPI score of 4-5 at initial diagnosis.Nine(9/56,16.1%)patients with DEL had MYD88 and CD79B mutations.Univariate analysis showed that age over 60 years(P=0.004),increasedβ2 microglobulin level(P=0.002),and high IPI score(P=0.003)were associated with poor overall survival(OS).Increasedβ2 microglobulin level(P=0.031),LDH level(P=0.017),stageⅢ-Ⅳ(P=0.001),high IPI score(P=0.013),immunohistochemical p53 mutation(P=0.049),and PIM1 mutation(P=0.039)were associated with poor progression-free survival(PFS).Multivariate analysis showed that IPI score of 4-5 was an independent risk factor for the prognosis of DEL(HR=2.622,95%CI 1.398-4.917,P=0.003).Survival analysis showed that there was a significant difference in the PFS between patients with DEL and those without DEL(65.6%vs 75.1%,P=0.002).However,there was no significant difference in the OS(81.8%vs 83.6%,P=0.226).In patients with DEL,the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen(81.5%vs 63.4%,P=0.004).Conclusion DEL is a group of aggressive lymphomas with relatively poor PFS.The R-EPOCH regimen may improve the overall prognosis of patients.