弥漫大B细胞淋巴瘤患者临床特征及预后分析

doi:10.3969/j.issn.1674-8115.2023.10.009

摘要/Abstract

摘要：

目的·分析弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma，DLBCL）患者临床特点和预后危险因素，评估自体造血干细胞移植（autologous stem cell transplantation，ASCT）及利妥昔单抗维持治疗对DLBCL患者预后的影响。方法·收集上海交通大学医学院附属新华医院血液科2015年1月—2020年1月收治的160例经病理及免疫分型初次确诊的DLBCL患者的临床资料，分析影响患者疗效与预后的危险因素。分析复发/难治性DLBCL患者的临床特征，评估挽救性ASCT对患者总生存（overall survival，OS）的影响。对中期评估达到完全缓解（complete remission，CR）的高危患者，评估ASCT及利妥昔单抗维持治疗对其生存预后的影响。结果·初治年龄>60岁（P=0.005）、国际预后指数（International Prognostic Index，IPI）3~5分（P=0.032）、低白蛋白水平（P=0.001）及贫血（P=0.007）患者的近期疗效不佳。多因素分析结果显示：患者初治年龄>60岁（HR=2.788，95%CI 1.575~4.936，P=0.000），non-GCB亚型（HR=2.230，95%CI 1.150~4.324，P=0.018），乳酸脱氢酶水平升高（HR=2.064，95%CI 1.006~4.234，P=0.048），低白蛋白水平（HR=2.052，95% CI 1.169~3.602，P=0.012）是影响患者无进展生存（progression-free survival，PFS）的独立危险因素；患者初治年龄>60岁（HR=2.269，95%CI 1.060~4.860，P=0.035），IPI评分3~5分（HR=2.557，95%CI 1.132~5.778，P=0.024）作为独立因素影响患者OS。对于复发/难治性DLBCL患者，挽救性ASCT能显著改善其预后，是患者死亡事件的保护性因素（P=0.030）。对于化学治疗后中期评估达到CR的高危患者，巩固性ASCT及利妥昔单抗维持治疗者至随访终点尚未出现死亡事件，但并未延长患者OS（P>0.05）。结论·挽救性ASCT能显著延长复发/难治性DLBCL患者OS，但巩固性ASCT及利妥昔单抗维持治疗并不能延长高危DLBCL患者OS。

关键词: 弥漫大B细胞淋巴瘤, 自体造血干细胞移植, 临床特征, 预后因素

Abstract:

Objective ·To analyze the clinical characteristics and prognostic risk factors of patients with diffuse large B-cell lymphoma (DLBCL), and evaluate the prognostic effects of autologous stem cell transplantation (ASCT) and rituximab maintenance therapy on DLBCL patients. Methods ·The clinical data of 160 patients with DLBCL who were first diagnosed by pathology and immunotyping were collected from the Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020, and the risk factors affecting the efficacy and prognosis of patients were analyzed. Moreover, the clinical characteristics of patients with relapsed/refractory DLBCL and the effect of salvage ASCT on overall survival (OS) were assessed. For those high-risk patients who achieved complete remission (CR) in the interim assessment, the impact of ASCT and rituximab maintenance therapy on survival outcomes was further assessed. Results ·Patients with initial age of treatment >60 years (P=0.005), International Prognostic Index (IPI) 3?5 scores (P=0.032), low albumin level (P=0.001) and anemia (P=0.007) had poor efficacy. Multivariate analysis showed that the initial age of treatment >60 years (HR=2.788, 95%CI 1.575?4.936, P=0.000), non-GCB subtype (HR=2.230, 95%CI 1.150?4.324, P=0.018), elevated lactate dehydrogenase level (HR=2.064, 95%CI 1.006?4.234, P=0.048) and low albumin level (HR=2.052, 95% CI 1.169?3.602, P=0.012) were the independent risk factors for progression-free survival (PFS). The initial age of treatment >60 years (HR=2.269, 95% CI 1.060?4.860, P=0.035) and IPI scores of 3 to 5 (HR=2.557, 95%CI 1.132?5.778, P=0.024) were independent factors affecting OS. For patients with relapsed/refractory DLBCL, salvage ASCT was found to significantly improve the prognosis of these patients and was a protective factor for the death event of patients (P=0.030). For patients in the high-risk group who achieved CR in the interim evaluation after chemotherapy, there were no deaths in patients on maintenance therapy with consolidation ASCT and rituximab to the end point of follow-up; however, it did not prolong the OS of the patients (P>0.05). Conclusion ·In patients with relapsed/refractory DLBCL, salvage ASCT can significantly prolong the OS, whereas in the high-risk patients of DLBCL, consolidation ASCT and rituximab maintenance therapy can't prolong the OS.

Key words: diffuse large B-cell lymphoma (DLBCL), autologous stem cell transplantation (ASCT), clinical feature, prognostic factor

中图分类号:

R557

赵洁, 姜言, 郝思国. 弥漫大B细胞淋巴瘤患者临床特征及预后分析[J]. 上海交通大学学报（医学版）, 2023, 43(10): 1282-1288.

ZHAO Jie, JIANG Yan, HAO Siguo. Clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(10): 1282-1288.

图/表 6

参考文献 21

1	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.
2	PFREUNDSCHUH M, KUHNT E, TRÜMPER L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group[J]. Lancet Oncol, 2011, 12(11): 1013-1022.
3	COIFFIER B, THIEBLEMONT C, VAN DEN NESTE E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte[J]. Blood, 2010, 116(12): 2040-2045.
4	GISSELBRECHT C, SCHMITZ N, MOUNIER N, et al. Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20⁺ diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma[J]. J Clin Oncol, 2012, 30(36): 4462-4469.
5	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.
6	YI J H, JEONG S H, KIM S J, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from two prospective Korean cohorts[J]. Cancer Res Treat, 2023, 55(1): 325-333.
7	GISSELBRECHT C, GLASS B, MOUNIER N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era[J]. J Clin Oncol, 2010, 28(27): 4184-4190.
8	CRUMP M, KURUVILLA J, COUBAN S, et al. Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: ncic-CTG LY.12[J]. J Clin Oncol, 2014, 32(31): 3490-3496.
9	EL-GALALY T C, CHEAH C Y, KRISTENSEN D, et al. Potentials, challenges and future of chimeric antigen receptor T-cell therapy in non-Hodgkin lymphomas[J]. Acta Oncol, 2020, 59(7): 766-774.
10	DREGER P, FENSKE T S, MONTOTO S, et al. Cellular immunotherapy for refractory diffuse large B cell lymphoma in the chimeric antigen receptor-engineered T cell era: still a role for allogeneic transplantation?[J]. Biol Blood Marrow Transplant, 2020, 26(4): e77-e85.
11	ALBANYAN O, CHAVEZ J, MUNOZ J. The role of CAR-T cell therapy as second line in diffuse large B-cell lymphoma[J]. Ther Adv Hematol, 2022, 13: 20406207221141511.
12	WANG T, XU L, GAO L, et al. Chimeric antigen receptor T-cell therapy combined with autologous stem cell transplantation improved progression-free survival of relapsed or refractory diffuse large B-cell lymphoma patients: a single-center, retrospective, cohort study[J]. Hematol Oncol, 2022, 40(4): 637-644.
13	ZINZANI P L, RODGERS T, MARINO D, et al. RE-MIND: comparing tafasitamab + lenalidomide (L-MIND) with a real-world lenalidomide monotherapy cohort in relapsed or refractory diffuse large B-cell lymphoma[J]. Clin Cancer Res, 2021, 27(22): 6124-6134.
14	HAMADANI M, RADFORD J, CARLO-STELLA C, et al. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma[J]. Blood, 2021, 137(19): 2634-2645.
15	PAPAGEORGIOU S G, THOMOPOULOS T P, LIASKAS A, et al. Monoclonal antibodies in the treatment of diffuse large B-cell lymphoma: moving beyond rituximab[J]. Cancers (Basel), 2022, 14(8): 1917.
16	BOURBON E, SALLES G. Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma[J]. Expert Opin Investig Drugs, 2020, 29(10): 1079-1088.
17	WULLENKORD R, BERNING P, NIEMANN A L, et al. The role of autologous stem cell transplantation (ASCT) in aggressive B-cell lymphomas: real-world data from a retrospective single-center analysis[J]. Ann Hematol, 2021, 100(11): 2733-2744.
18	EPPERLA N, HAMADANI M, RELJIC T, et al. Upfront autologous hematopoietic stem cell transplantation consolidation for patients with aggressive B-cell lymphomas in first remission in the rituximab era: a systematic review and meta-analysis[J]. Cancer, 2019, 125(24): 4417-4425.
19	HUANG H H, WEN Y C, CHEN H M, et al. Rituximab maintenance improves overall survival in follicular lymphoma: a retrospective nationwide real-world analysis from Taiwan Cancer Registry Database[J]. Cancer Med, 2018, 7(8): 3582-3591.
20	HALWANI A S, RASMUSSEN K M, PATIL V, et al. Maintenance rituximab in veterans with follicular lymphoma[J]. Cancer Med, 2020, 9(20): 7537-7547.
21	ZHOU X, MA T, ZHANG Y, et al. Rituximab maintenance therapy for patients with diffuse large B-cell lymphoma: a meta-analysis[J]. PLoS One, 2017, 12(3): e0174648.

编辑推荐 0

Metrics

阅读次数

全文

500

HTML			PDF

最新录用	在线预览	正式出版	最新录用	在线预览	正式出版
0	0	20	0	0	480

来源	本网站	其他网站

次数	324	176
比例	65%	35%

摘要

511

最新录用	在线预览	正式出版

0	0	511

来源	本网站	其他网站

次数	354	157
比例	69%	31%

Variable	Patients/n(%)
Gender
Male	88 (55.0)
Female	72 (45.0)
Age
≤60 years	73 (45.6)
>60 years	87 (54.4)
Group B symptoms
No	87 (54.4)
Yes	73 (45.6)
Hans classification
GCB	56 (35.0)
Non-GCB	104 (65.0)
ECOG score
<2 scores	117 (73.1)
≥2 scores	43 (26.9)
Ann Arbor stage
Ⅰ‒Ⅱ	63 (39.4)
Ⅲ‒Ⅳ	97 (60.6)
IPI score
0‒2 scores	70 (43.8)
3‒5 scores	90 (56.2)
LDH level
≤211 U·L^-1	51 (31.9)
>211 U·L^-1	109 (68.1)
Albumin level
≥35 g·L^-1	123 (76.9)
<35 g·L^-1	37 (23.1)
Absolute lymphocyte level
>1.1×10⁹·L^-1	104 (65.0)
≤1.1×10⁹·L^-1	56 (35.0)
Anemia
No	106 (66.2)
Yes	54 (33.8)
Chemotherapy regimen
R-CHOP	147 (91.9)
CHOP	13 (8.1)

Variable	Patients/n(%)
Gender
Male	88 (55.0)
Female	72 (45.0)
Age
≤60 years	73 (45.6)
>60 years	87 (54.4)
Group B symptoms
No	87 (54.4)
Yes	73 (45.6)
Hans classification
GCB	56 (35.0)
Non-GCB	104 (65.0)
ECOG score
<2 scores	117 (73.1)
≥2 scores	43 (26.9)
Ann Arbor stage
Ⅰ‒Ⅱ	63 (39.4)
Ⅲ‒Ⅳ	97 (60.6)
IPI score
0‒2 scores	70 (43.8)
3‒5 scores	90 (56.2)
LDH level
≤211 U·L^-1	51 (31.9)
>211 U·L^-1	109 (68.1)
Albumin level
≥35 g·L^-1	123 (76.9)
<35 g·L^-1	37 (23.1)
Absolute lymphocyte level
>1.1×10⁹·L^-1	104 (65.0)
≤1.1×10⁹·L^-1	56 (35.0)
Anemia
No	106 (66.2)
Yes	54 (33.8)
Chemotherapy regimen
R-CHOP	147 (91.9)
CHOP	13 (8.1)

Variable	Overall response rate (CR+PR)
Variable	Patients/n(%)	P value
Gender
Male	74/88 (84.1)	0.381
Female	64/72 (88.9)
Age
≤60 years	69/73 (94.5)	0.005
>60 years	69/87 (79.3)
Group B symptoms
No	79/87 (90.8)	0.068
Yes	59/73 (80.8)
Hans classification
GCB	51/56 (91.1)	0.194
Non-GCB	87/104 (89.7)
ECOG score
<2 scores	104/117 (88.9)	0.110
≥2 scores	34/43 (79.1)
Ann Arbor stage
Ⅰ‒Ⅱ	57/63 (90.5)	0.211
Ⅲ‒Ⅳ	81/97 (83.5)
IPI score
0‒2 scores	65/70 (92.9)	0.032
3‒5 scores	73/90 (81.1)
LDH level
≤211 U·L^-1	47/51 (92.2)	0.138
>211 U·L^-1	91/109 (83.5)
Albumin level
≥35 g·L^-1	112/123 (91.1)	0.001
<35 g·L^-1	26/37 (70.3)
Absolute lymphocyte level
>1.1×10⁹·L^-1	93/104 (89.4)	0.112
≤1.1×10⁹·L^-1	45/56 (80.4)
Anemia
No	97/106 (91.5)	0.007
Yes	41/54 (75.9)
Chemotherapy regimen
R-CHOP	126/147 (85.7)	0.508
CHOP	12/13 (92.3)

Variable	Overall response rate (CR+PR)
Variable	Patients/n(%)	P value
Gender
Male	74/88 (84.1)	0.381
Female	64/72 (88.9)
Age
≤60 years	69/73 (94.5)	0.005
>60 years	69/87 (79.3)
Group B symptoms
No	79/87 (90.8)	0.068
Yes	59/73 (80.8)
Hans classification
GCB	51/56 (91.1)	0.194
Non-GCB	87/104 (89.7)
ECOG score
<2 scores	104/117 (88.9)	0.110
≥2 scores	34/43 (79.1)
Ann Arbor stage
Ⅰ‒Ⅱ	57/63 (90.5)	0.211
Ⅲ‒Ⅳ	81/97 (83.5)
IPI score
0‒2 scores	65/70 (92.9)	0.032
3‒5 scores	73/90 (81.1)
LDH level
≤211 U·L^-1	47/51 (92.2)	0.138
>211 U·L^-1	91/109 (83.5)
Albumin level
≥35 g·L^-1	112/123 (91.1)	0.001
<35 g·L^-1	26/37 (70.3)
Absolute lymphocyte level
>1.1×10⁹·L^-1	93/104 (89.4)	0.112
≤1.1×10⁹·L^-1	45/56 (80.4)
Anemia
No	97/106 (91.5)	0.007
Yes	41/54 (75.9)
Chemotherapy regimen
R-CHOP	126/147 (85.7)	0.508
CHOP	12/13 (92.3)

Variable	Univariate analysis		Multivariate analysis
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Female	0.668 (0.394‒1.132)	0.134
Age>60 years	2.744 (1.553‒4.848)	0.001	2.788 (1.575‒4.936)	0.000
Group B symptoms	1.424 (0.850‒2.386)	0.179
Non-GCB	2.398 (1.243‒4.624)	0.009	2.230 (1.150‒4.324)	0.018
ECOG score ≥2	2.330 (1.379‒3.937)	0.002
Ann Arbor stage Ⅲ‒Ⅳ	2.496 (1.366‒4.561)	0.003
IPI score 3‒5	3.149 (1.722‒5.759)	0.000
Increased LDH [>211 U·L^-1]	2.796 (1.413‒5.535)	0.003	2.064 (1.006‒4.234)	0.048
Low albumin [<35 g·L^-1]	2.824 (1.657‒4.811)	0.000	2.052 (1.169‒3.602)	0.012
Lymphocytopenia (≤1.1×10⁹·L^-1)	2.142 (1.277‒3.592)	0.004
Anemia	1.894 (1.128‒3.179)	0.016
Chemotherapy (R-CHOP)	0.937 (0.400‒2.195)	0.881