525例弥漫大B细胞淋巴瘤预后影响因素分析

摘要/Abstract

摘要： 目的：描述弥漫大B细胞淋巴瘤（diffuse large B cell lymphoma, DLBCL）的临床特征、生存情况，探讨预后相关因素。方法:回顾性分析1995年1月至2008年12月在北京大学肿瘤医院初治、资料完整的DLBCL病例。构建Kaplan-Meier生存曲线，估计5年总生存率，对选取的参数进行单因素分析，各组生存率（时期生存率）比较用Log-rank 检验；各因素 5年生存率（时点生存率）的比较用U检验，采用Cox模型对单因素分析有统计学意义的参数进行多因素回归分析（采用后退法），多因素分析以双侧95%CI为统计标准，Cox模型中以P<0.05为差异有统计学意义。结果:共收集到资料完整的DLBCL病例525例，其中男性294例（56.0%），女性231例（44.0%）。发病中位年龄55（16~90）岁，>60岁者194例（37.0%）。Ann Arbor分期：Ⅰ期54例（10.3%）、Ⅱ期152例（28.9%）、Ⅲ期117例（22.3%）、Ⅳ期202例（38.5%）。起病时有B症状者206例（39.2%），血清LDH升高者192例（36.6%）。治疗过程中联合利妥昔单抗（rituximab,R）和未联合利妥昔单抗（non-R）治疗的病例分别为197例（37.5%）和328（62.5%）。全组中位随访时间77.5（0~205）个月，中位总生存期84个月，5年总生存率52.3%。无论单因素分析还是多因素分析均显示以下因素具有统计学意义：年龄60岁分界、性别、Ann Arbor分期、有无B症状、血清LDH升高与否、治疗中是否联合利妥昔单抗（R组和non-R组）。相对风险度(RR)分别为：RR(发病年龄>60岁/≤60岁)=1.380（95%CI 1.078~1.765），RR(男性/女性)=1.315（95%CI 1.025~1.687），RR(Ⅲ期/Ⅰ期)=3.034（95%CI 1.667~5.522），RR(Ⅳ期/Ⅰ期)=3.748（95%CI 2.102~6.681）、RR(有B症状/无B症状)=1.278（95%CI 0.999~1.636)、RR(血清LDH水平未升高/升高)=1.351（95%CI 1.057~1.726），RR(nonR/R)=1.543（95%CI 1.182~2.015）。将年龄分界下移到50岁，单因素与多因素分析显示其可预测预后，RR=1.478 (95% CI 1.148~1. 902）,P=0.002。结论：性别、年龄、初诊分期、B症状、LDH水平、是否使用利妥昔单抗治疗与DLBCL的预后存在关系；与IPI评分系统相比，性别、年龄分界下移到50岁、B症状可能是中国DLBCL患者比较独特的预后因素，但仍需大样本、多中心、多地区数据进一步研究。

关键词: 预后, 淋巴瘤, 大B细胞, 弥漫性, Kaplan-Meiers评估

Abstract: Objective：To describe the clinical characteristics, overall survival as well as to evaluate the prognostic factors in Chinese diffuse large B cell lymphoma (DLBCL) patients.Methods: DLBCL patients who were initially diagnosed and treated in Peking University Cancer Hospital from January 1995 to December 2008 were identified and analyzed,retrospectively.The 5-year OS rates were estimated with Kaplan-Meier.Log-rank test was used to compare the survival curves of the different groups. The multivariate analysis of prognostic factors was conducted with Cox regression model, which included all statistically significant prognostic factors in the univariate analyses.Results: A total of 525 DLBCL patients were included in this retrospective analysis, of whom, 294 were male and 231 female (male∶ female=1.27∶1). The median age at the initial diagnosis was 55 (range 16-90) years, and 37.0% (n=194) were 60 years and above. Regarding the clinical staging at the initial diagnosis, 54 patients (10.3%) were diagnosed as Stage Ⅰ of the disease, 152 (28.9%) as Stage Ⅱ, 117 (22.3%) as Stage Ⅲ and 202 (38.5%) as Stage Ⅳ. The ‘B symptoms’ and increased serum LDH were presented in 206 (39.2%) and 192 (36.6%) patients, respectively. A total of 197 (37.5%) patients were treated with rituximab (R). The survival follow-up continued till 31 January 2014 with a median follow-up time of 77.5 (range: 0-205) months. A total of 267 patients (50.9%) died during the follow-up period. The medial overall survival (OS) time was 84 months, and 5-year OS rate was 52.3%. There were six statistically significant prognostic factors that were identified in both univariate and multivariate analyses: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. The relative risk (RR) of these prognostic factors in the multivariate analyses were: age >60 years / ≤60 years=1.380 (95%CI 1.078-1.765), male / female=1.315 (95%CI 1.025-1.687), stage Ⅲ/stage Ⅰ=3.034(95%CI 1.667-5.522), stage Ⅳ/Ⅰ=3.748(95%CI 2.102-6.681), with B symptoms/without B symptoms=1.278(95%CI 0.999-1.636),serum LDH increased/LDH not increased=1.351(95%CI 1.057-1.726), without R treatment / with R treatment=1.543(95%CI 1.182-2.015).Compared with the IPI, age >50 years/≤50 years was a statistically significant factor in both univariate and multivariate analyses RR=1.478 (95%CI 1.148-1. 902）, P=0.002.Conclusion:Six factors were related to DLBCL survival: gender, Ann Arbor stage, B symptom, serum LDH, age at initial diagnosis and rituximab treatment. Compared with the IPI, several specific factors may predict a poor prognosis in Chinese DLBCL patients: male, age>50 years and the presence of ‘B symptoms’. But this result is not conclusive until these factors are further tested.

Key words: Prognosis, Lymphoma, large B-cell diffuse, Kaplan-Meiers estimate

傅志英, 朱军, 宋玉琴, 刘卫平, 季新强, 詹思延. 525例弥漫大B细胞淋巴瘤预后影响因素分析[J]. 北京大学学报（医学版）, 2014, 46(3): 405-411.

FU Zhi-Ying, ZHU Jun, SONG Yu-Qin, LIU Wei-Ping, JI Xin-Qiang, ZHAN Si-Yan. Prognostic analysis of 525 Chinese patients with diffuse large B cell lymphoma[J]. Journal of Peking University(Health Sciences), 2014, 46(3): 405-411.

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