上海交通大学学报(医学版) ›› 2023, Vol. 43 ›› Issue (10): 1282-1288.doi: 10.3969/j.issn.1674-8115.2023.10.009
• 论著 · 临床研究 • 上一篇
收稿日期:
2023-04-24
接受日期:
2023-08-01
出版日期:
2023-10-28
发布日期:
2023-10-28
通讯作者:
郝思国
E-mail:1805941747@qq.com;haosiguo@xinhuamed.com.cn
作者简介:
赵 洁(1996—),女,住院医师,硕士;电子信箱:1805941747@qq.com。
ZHAO Jie(), JIANG Yan, HAO Siguo(
)
Received:
2023-04-24
Accepted:
2023-08-01
Online:
2023-10-28
Published:
2023-10-28
Contact:
HAO Siguo
E-mail:1805941747@qq.com;haosiguo@xinhuamed.com.cn
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。
中图分类号:
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.
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) |
表1 DLBCL患者基本临床特征 (n=160)
Tab 1 General clinical features of patients with DLBCL (n=160)
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) | |
---|---|---|
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) |
表2 DLBCL患者近期疗效分析
Tab 2 Analysis of short-term efficacy of patients with DLBCL
Variable | Overall response rate (CR+PR) | |
---|---|---|
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 | |||
---|---|---|---|---|---|
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 |
表 3 影响DLBCL患者PFS 的单因素和多因素分析
Tab 3 Univariate and multivariate analysis for the factors affecting PFS of patients with DLBCL
Variable | Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|---|
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 |
Variable | Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|---|
HR(95%CI) | P value | HR(95%CI) | P value | ||
Female | 0.586 (0.296‒1.158) | 0.124 | |||
Age>60 years | 2.950 (1.416‒6.145) | 0.004 | 2.269 (1.060‒4.860) | 0.035 | |
Group B symptoms | 1.283 (0.667‒2.468) | 0.455 | |||
Non-GCB | 1.515 (0.712‒3.223) | 0.281 | |||
ECOG score ≥2 | 2.122 (1.092‒4.124) | 0.027 | |||
Ann Arbor stage Ⅲ‒Ⅳ | 2.295 (1.078‒4.888) | 0.031 | |||
IPI score 3‒5 | 3.261 (1.484‒7.166) | 0.003 | 2.557 (1.132‒5.778) | 0.024 | |
Increased LDH [>211 U·L-1] | 3.422 (1.329‒8.808) | 0.011 | |||
Low albumin [<35 g·L-1] | 2.423 (1.238‒4.745) | 0.010 | |||
Lymphocytopenia (≤1.1×109·L-1) | 1.760 (0.911‒3.402) | 0.093 | |||
Anemia | 1.720 (0.891‒3.320) | 0.106 | |||
Chemotherapy (R-CHOP) | 1.422 (0.431‒4.699) | 0.563 |
表4 影响 DLBCL患者OS的单因素和多因素分析
Tab 4 Univariate and multivariate analysis for the factors affecting OS of patients with DLBCL
Variable | Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|---|
HR(95%CI) | P value | HR(95%CI) | P value | ||
Female | 0.586 (0.296‒1.158) | 0.124 | |||
Age>60 years | 2.950 (1.416‒6.145) | 0.004 | 2.269 (1.060‒4.860) | 0.035 | |
Group B symptoms | 1.283 (0.667‒2.468) | 0.455 | |||
Non-GCB | 1.515 (0.712‒3.223) | 0.281 | |||
ECOG score ≥2 | 2.122 (1.092‒4.124) | 0.027 | |||
Ann Arbor stage Ⅲ‒Ⅳ | 2.295 (1.078‒4.888) | 0.031 | |||
IPI score 3‒5 | 3.261 (1.484‒7.166) | 0.003 | 2.557 (1.132‒5.778) | 0.024 | |
Increased LDH [>211 U·L-1] | 3.422 (1.329‒8.808) | 0.011 | |||
Low albumin [<35 g·L-1] | 2.423 (1.238‒4.745) | 0.010 | |||
Lymphocytopenia (≤1.1×109·L-1) | 1.760 (0.911‒3.402) | 0.093 | |||
Anemia | 1.720 (0.891‒3.320) | 0.106 | |||
Chemotherapy (R-CHOP) | 1.422 (0.431‒4.699) | 0.563 |
Variable | Death rate | |
---|---|---|
Patients/n(%) | P value | |
Gender | ||
Male | 23/35 (65.7) | 0.570 |
Female | 11/19 (57.9) | |
Age | ||
≤60 years | 9/16 (56.3) | 0.507 |
>60 years | 25/38 (65.8) | |
Group B symptoms | ||
No | 17/25 (68.0) | 0.477 |
Yes | 17/29 (58.6) | |
Hans classification | ||
GCB | 8/10 (80.0) | 0.383 |
Non-GCB | 26/44 (59.1) | |
ECOG score | ||
<2 scores | 20/31 (64.5) | 0.784 |
≥2 scores | 14/23 (60.9) | |
Ann Arbor stage | ||
Ⅰ‒Ⅱ | 8/12 (66.7) | 1.000 |
Ⅲ‒Ⅳ | 26/42 (61.9) | |
IPI score | ||
0‒2 scores | 7/12 (58.3) | 0.970 |
3‒5 scores | 27/42 (64.3) | |
LDH level | ||
≤211 U·L-1 | 4/8 (50.0) | 0.670 |
>211 U·L-1 | 30/46 (65.2) | |
Albumin level | ||
≥35 g·L-1 | 20/32 (62.5) | 0.932 |
<35 g·L-1 | 14/22 (63.6) | |
Absolute lymphocyte level | ||
>1.1×109·L-1 | 19/27 (70.4) | 0.260 |
≤1.1×109·L-1 | 15/27 (55.6) | |
Anemia | ||
No | 19/29 (65.5) | 0.675 |
Yes | 15/25 (60.0) | |
ASCT | ||
Yes | 0/4 (0) | 0.030 |
No | 34/50 (68.0) |
表5 复发/难治性DLBCL患者死亡的危险因素分析
Tab 5 Risk factor analysis for death in patients with relapsed/refractory DLBCL
Variable | Death rate | |
---|---|---|
Patients/n(%) | P value | |
Gender | ||
Male | 23/35 (65.7) | 0.570 |
Female | 11/19 (57.9) | |
Age | ||
≤60 years | 9/16 (56.3) | 0.507 |
>60 years | 25/38 (65.8) | |
Group B symptoms | ||
No | 17/25 (68.0) | 0.477 |
Yes | 17/29 (58.6) | |
Hans classification | ||
GCB | 8/10 (80.0) | 0.383 |
Non-GCB | 26/44 (59.1) | |
ECOG score | ||
<2 scores | 20/31 (64.5) | 0.784 |
≥2 scores | 14/23 (60.9) | |
Ann Arbor stage | ||
Ⅰ‒Ⅱ | 8/12 (66.7) | 1.000 |
Ⅲ‒Ⅳ | 26/42 (61.9) | |
IPI score | ||
0‒2 scores | 7/12 (58.3) | 0.970 |
3‒5 scores | 27/42 (64.3) | |
LDH level | ||
≤211 U·L-1 | 4/8 (50.0) | 0.670 |
>211 U·L-1 | 30/46 (65.2) | |
Albumin level | ||
≥35 g·L-1 | 20/32 (62.5) | 0.932 |
<35 g·L-1 | 14/22 (63.6) | |
Absolute lymphocyte level | ||
>1.1×109·L-1 | 19/27 (70.4) | 0.260 |
≤1.1×109·L-1 | 15/27 (55.6) | |
Anemia | ||
No | 19/29 (65.5) | 0.675 |
Yes | 15/25 (60.0) | |
ASCT | ||
Yes | 0/4 (0) | 0.030 |
No | 34/50 (68.0) |
图1 ASCT及利妥昔单抗维持治疗的DLBCL患者的生存曲线与生存分析Note: A. OS curve of relapsed/refractory DLBCL patients with ASCT (Log-rank P=0.019). B. OS curve of ASCT or rituximab maintenance therapy in patients in the high-risk group with CR who had achieved interim assessment (ASCT vs no consolidation therapy, Log-rank P=0.361; rituximab maintenance vs no consolidation therapy, Log-rank P=0.546. There was no significant difference among the three groups, P=0.511).
Fig1 Survival curves and survival analysis of patients with ASCT or rituximab maintenance therapy
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