肾脏累及的弥漫性大B细胞淋巴瘤患者临床病理特征

doi:10.3969/j.issn.1674-8115.2024.09.011

上海交通大学学报（医学版） ›› 2024, Vol. 44 ›› Issue (9): 1162-1168.doi: 10.3969/j.issn.1674-8115.2024.09.011

• 论著 · 临床研究 • 上一篇

肾脏累及的弥漫性大B细胞淋巴瘤患者临床病理特征

王博恩(), 陈思远, 施晴, 张慕晨, 易红梅, 董磊, 王黎, 程澍, 许彭鹏(), 赵维莅

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试验室，上海血液学研究所，上海 200025

收稿日期:2024-04-29 接受日期:2024-08-03 出版日期:2024-09-28 发布日期:2024-10-09
通讯作者: 许彭鹏 E-mail:wangboen@sjtu.edu.cn;pengpeng_xu@126.com
作者简介:王博恩（2000—），男，硕士生；电子信箱：wangboen@sjtu.edu.cn。
基金资助:
国家自然科学基金(82130004);上海交通大学医学院“双百人”项目(20230013)

Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma

WANG Boen(), CHEN Siyuan, SHI Qing, ZHANG Muchen, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng(), ZHAO Weili

Department of Hematology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine; State Key Laboratory of Medical Genomics; Shanghai Institute of Hematology, Shanghai 200025, China

Received:2024-04-29 Accepted:2024-08-03 Online:2024-09-28 Published:2024-10-09
Contact: XU Pengpeng E-mail:wangboen@sjtu.edu.cn;pengpeng_xu@126.com
Supported by:
National Natural Science Foundation of China(82130004);“Two-hundred Talents” Program of Shanghai Jiao Tong University School of Medicine(20230013)

摘要/Abstract

摘要：

目的·探究肾脏累及的弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）患者的临床病理特征，包括临床基本信息、病理特征、基因突变谱与预后相关因素等。方法·回顾性分析2005年7月—2021年11月上海交通大学医学院附属瑞金医院收治的149例肾脏累及的DLBCL患者的临床资料，包括治疗方案、疗效评价及分期等，并采用靶向测序（54个淋巴瘤相关基因）评估患者的基因突变情况。基于患者资料进行生存和预后因素分析。结果·在149例DLBCL肾脏累及的患者中，有87例患者（58.4%）年龄>60岁，121例患者（81.2%）Ann Arbor分期为Ⅲ~Ⅳ期，27例患者（18.1%）美国东部肿瘤协作组评分≥2分，121例患者（81.2%）血清乳酸脱氢酶（lactate dehydrogenase，LDH）高于正常上限，111例患者（74.5%）至少存在2个以上淋巴结外器官受累，131例患者（87.9%）国际预后指数≥2分。患者的5年总生存率和5年无进展生存率分别为52.2%和50.4%。在病理特征中，145例患者（97.3%）诊断为非特指型DLBCL。按Hans分型，39例患者（26.2%）属生发中心亚型。在可评估疗效的144例患者中，87例（60.4%）患者取得完全缓解。此外，单因素分析显示：血清LDH升高是肾脏累及的DLBCL患者总体生存时间（P=0.048）和无进展生存时间（P=0.033）的不良预后因素；75例肾脏累及的DLBCL患者的靶向测序显示PIM1（n=23，31%）、MYD88（n=22，29%）、CD79B（n=21，28%）和KMT2D（n=18，24%）存在高频突变，其中CD79B突变与较差的总体生存时间相关（P=0.034）。结论·肾脏累及的DLBCL患者临床特征中血清LDH升高与不良预后有关，基因突变谱中CD79B突变与不良预后有关。

关键词: 弥漫性大B细胞淋巴瘤, 肾脏, 临床特征, 基因突变谱, 预后分析

Abstract:

Objective ·To analyze the clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma (DLBCL), including clinical characteristics, pathological characteristics, gene mutation profiles, and prognostic factors. Methods ·One hundred and forty-nine patients with kidney-involved DLBCL, admitted to Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from July 2005 to November 2021, were retrospectively analyzed for their clinicopathological data, survival and prognostic factors, which included therapeutic methods, clinical outcomes, staging, etc. Gene mutation profiles were evaluated by targeted sequencing of 54 lymphoma-related genes. Prognostic factors were also analyzed based on the information mentioned above. Results ·A total of 149 kidney-involved DLBCL cases were included, of which 89 patients (58.4%) were aged over sixty, 121 patients (81.2%) were staged Ann Arbor Ⅲ?Ⅳ, 27 patients (18.1%) had an Eastern Cooperative Oncology Group (ECOG) performance status of two or more, 121 patients (81.2%) had elevated serum lactate dehydrogenase (LDH) level, 111 patients (74.5%) had extranodal invasion in at least two organs and 131 patients (87.9%) scored over 2 points on the international prognosis index (IPI). The estimated 5-year overall survival (OS) rate and progression-free survival (PFS) rate of kidney-involved DLBCL patients were 52.2% and 50.4% respectively. Univariate analysis revealed that elevated serum LDH levels were an adverse prognostic factor for both OS (P=0.048) and PFS (P=0.033). In pathological characteristics, 145 patients (97.3%) belonged to DLBCL, not otherwise specified (NOS) and 39 patients (26.3%) belonged to germinal center B-cell (GCB) according to Hans classification. Among 144 patients who could be evaluated for clinical outcomes, 87 patients (60.4%) got complete response (CR). Targeted sequencing data from 75 kidney-involved DLBCL patients showed high mutation frequency in PIM1 (n=23, 31%), MYD88 (n=22, 29%), CD79B (n=21, 28%) and KMT2D (n=18, 24%), with CD79B mutation indentified as an adverse prognostic factor for OS in patients with kidney-involved DLBCL (P=0.034). Conclusion ·Elevated serum LDH level is an adverse prognostic factor in patients with kidney-involved DLBCL. The prognosis of patients with CD79B mutations is poor.

Key words: diffuse large B-cell lymphoma (DLBCL), kidney, clinic pathologic characteristics, gene mutation profile, prognosis

中图分类号:

R733.4

王博恩, 陈思远, 施晴, 张慕晨, 易红梅, 董磊, 王黎, 程澍, 许彭鹏, 赵维莅. 肾脏累及的弥漫性大B细胞淋巴瘤患者临床病理特征[J]. 上海交通大学学报（医学版）, 2024, 44(9): 1162-1168.

WANG Boen, CHEN Siyuan, SHI Qing, ZHANG Muchen, YI Hongmei, DONG Lei, WANG Li, CHENG Shu, XU Pengpeng, ZHAO Weili. Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(9): 1162-1168.

图/表 6

表1 肾脏累及的DLBCL患者临床特征分析［n（%）， N=149］

Tab 1 Analysis of clinical characteristics of patients with kidney-involved DLBCL ［n（%）， N=149］

Chatacteristic	n (%)
Age of diagnose
≤60/years	62 (41.6)
>60/years	87 (58.4)
Ann Arbor stage
Ⅰ‒Ⅱ	28 (18.8)
Ⅲ‒Ⅳ	121 (81.2)
ECOG
0‒1 score	122 (81.9)
≥2 score	27 (18.1)
Serum LDH
Normal	28 (18.8)
Elevated	121 (81.2)
Extranodal involvement
0‒1	38 (25.5)
≥2	111 (74.5)
IPI
0‒1 score	18 (12.1)
2‒5 score	131 (87.9)
Pathological subtype
DLBCL, NOS	145 (97.3)
HGBCL with MYC and BCL2/BCL6 rearrangement	4 (2.7)
Hans classification
GCB	39 (26.2)
non-GCB	90 (60.4)
Unknown	20 (13.4)
MYC and BCL2 double expressor
Yes	36 (24.2)
No	113 (75.8)
Outcome^①
CR	87 (60.4)
PR	11 (7.6)
SD/PD	46 (31.9)
Unknown	5 (3.4)

图1 肾脏累及的DLBCL患者的OS（A）和PFS（B）曲线Note： A. OS curve in patients with kidney-involved DLBCL. B. PFS curve in patients with kidney-involved DLBCL.

Fig 1 The curves of OS (A) and PFS (B) in patients with kidney-involved DLBCL

表2 肾脏累及的DLBCL患者预后的单因素分析

Tab 2 Univariate analysis in patients with kidney-involved DLBCL

Characteristic	OS		PFS
Characteristic	HR (95%CI)	P value	HR (95%CI)	P value
Age (>60 years)	1.514 (0.914‒2.508)	0.108	1.359 (0.821‒2.251)	0.233
ECOG score (≥2 score)	1.675 (0.939‒2.986)	0.081	1.487 (0.809‒2.733)	0.202
Ann Arbor (Ⅲ‒Ⅳ)	1.119 (0.607‒2.060)	0.719	1.257 (0.657‒2.046)	0.489
Elevated serum LDH	2.045 (1.018‒4.151)	0.048	2.241 (1.067‒4.704)	0.033
Extranodal involvement≥2	1.069 (0.621‒1.843)	0.809	1.600 (0.871‒2.941)	0.130
Hans (non-GCB)	1.577 (0.969‒2.568)	0.067	1.361 (0.834‒2.220)	0.217
MYC and BCL2 double expressor	1.210 (0.574‒2.552)	0.616	1.073 (0.543‒2.121)	0.839

图2 肾脏累及的DLBCL患者LDH水平与OS（A）和PFS（B）的关系Note： A. Relationship between LDH level and OS in patients with kidney-involved DLBCL. B. Relationship between LDH level and PFS in patients with kidney-involved DLBCL.

Fig 2 The relationship between LDH level and OS (A) or PFS (B) in patients with kidney-involved DLBCL

图3 肾脏累及的DLBCL患者的基因突变图谱

Fig 3 Gene mutation profiles in patients with kidney-involved DLBCL

图4 肾脏累及的DLBCL患者 CD79B 基因的突变状态与OS（A）和PFS（B）的关系Note： A. Relationship between CD79B mutation and OS in patients with kidney-involved DLBCL. B. Relationship between CD79B mutation and PFS in patients with kidney-involved DLBCL.

Fig 4 The relationship between CD79B gene mutation and OS (A) or PFS (B) in patients with kidney DLBCL

参考文献 13

1	SUSANIBAR-ADANIYA S, BARTA S K. 2021 Update on Diffuse large B cell lymphoma: a review of current data and potential applications on risk stratification and management[J]. Am J Hematol, 2021, 96(5): 617-629.
2	SEHN L H, SALLES G. Diffuse large B-cell lymphoma[J]. N Engl J Med, 2021, 384(9): 842-858.
3	VILLA D, CONNORS J M, SEHN L H, et al. Diffuse large B-cell lymphoma with involvement of the kidney: outcome and risk of central nervous system relapse[J]. Haematologica, 2011, 96(7): 1002-1007.
4	SHI Y K, HAN Y, YANG J L, et al. Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin: analysis of 1, 085 WHO classified cases in a single institution in China[J]. Chin J Cancer Res, 2019, 31(1): 152-161.
5	SWERDLOW S H, CAMPO E, PILERI S A, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J]. Blood, 2016, 127(20): 2375-2390.
6	CHESON B D, FISHER R I, BARRINGTON S F, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification[J]. J Clin Oncol, 2014, 32(27): 3059-3068.
7	ZHU J, MA J, Union for China Lymphoma Investigators of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for malignant lymphoma 2021 (English version)[J]. Chin J Cancer Res, 2021, 33(3): 289-301.
8	ZHU Y, FU D, SHI Q, et al. Oncogenic mutations and tumor microenvironment alterations of older patients with diffuse large B-cell lymphoma[J]. Front Immunol, 2022, 13: 842439.
9	SHEN R, XU P P, WANG N, et al. Influence of oncogenic mutations and tumor microenvironment alterations on extranodal invasion in diffuse large B-cell lymphoma[J]. Clin Transl Med, 2020, 10(7): e221.
10	LEHNERS N, KRÄMER I, SCHWARZBICH M A, et al. Analysis of clinical characteristics and outcome of patients with previously untreated diffuse large B-cell lymphoma and renal involvement in the rituximab era[J]. Leuk Lymphoma, 2016, 57(11): 2619-2625.
11	OLLILA T A, OLSZEWSKI A J. Extranodal diffuse large B cell lymphoma: molecular features, prognosis, and risk of central nervous system recurrence[J]. Curr Treat Options Oncol, 2018, 19(8): 38.
12	WRIGHT G W, HUANG D W, PHELAN J D, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications[J]. Cancer Cell, 2020, 37(4): 551-568.e14.
13	WILSON W H, WRIGHT G W, HUANG D W, et al. Effect of ibrutinib with R-CHOP chemotherapy in genetic subtypes of DLBCL[J]. Cancer Cell, 2021, 39(12): 1643-1653.e3.

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肾脏累及的弥漫性大B细胞淋巴瘤患者临床病理特征

Clinicopathologic characteristics of patients with kidney-involved diffuse large B-cell lymphoma

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