血管免疫母细胞性T细胞淋巴瘤患者外周血淋巴细胞亚群检测的临床意义

doi:10.3969/j.issn.1004-583X.2022.11.007

摘要/Abstract

摘要：

目的分析血管免疫母细胞性T细胞淋巴瘤(AITL)患者诊断时外周血淋巴细胞亚群与临床预后的相关性及其化疗后的动态变化。方法回顾性分析2016年3月至2021年9月就诊于苏州大学附属第三医院的16例初治AITL患者的临床资料,以同期10例健康人群的淋巴细胞亚群结果为对照组。采用Kaplan-Meier法及COX回归模型进行生存分析。采用ROC曲线计算CD4/CD8临界值,并将患者分为低CD4/CD8组和高CD4/CD8组。结果与对照组相比,AITL患者诊断时外周血中CD3⁺T细胞、CD4⁺T细胞、CD3⁺CD25⁺活化T细胞计数及CD4/CD8比值明显降低;同时,CD19⁺B细胞、CD20⁺B细胞、CD5⁺CD19⁺及CD19⁺CD23⁺活化B细胞计数皆明显降低。在第一疗程化疗后,患者CD3⁺T细胞比例较初诊时明显升高,在完成3疗程治疗后,CD4⁺T细胞比例、CD3⁺CD25⁺活化T细胞比例及CD4/CD8比值明显升高。生存分析显示低CD4/CD8组无进展生存时间(PFS)及总生存期(OS)均明显优于高CD4/CD8组。结论 AITL患者初诊时外周血中高CD4/CD8比值与临床不良预后相关。与健康人群相比,AITL患者外周血CD4⁺ T细胞计数明显降低,且在有效治疗后可部分恢复。通过对AITL患者淋巴细胞亚群的分析,能够为识别AITL新的预后标志及实施有效的个体化免疫治疗提供新的思路。

关键词: 淋巴瘤, T细胞, 淋巴细胞亚群, CD4⁺T细胞, CD4/CD8

Abstract:

Objective To analyze the relevance between lymphocyte subsets and clinical prognosis in the peripheral blood of patients with angioimmunoblastic T cell lymphoma (AITL) during diagnosis, and to assess their dynamic changes after chemotherapy.M-ethods The clinical data of 16 initial AITL patients (treatment group) and 10 lymphocyte subsets (control group) were retrospectively analyzed, these patients visited the Third Affiliated Hospital of Soochow University between March 2016 and September 2021. Kaplan-Meier method and Cox regression were adopted for survival analysis. Receiver Operator Characteristic (ROC)curve was used to calculate the cutoff value of CD4/CD8 ratio, and the patients of the treatment group were assigned into low and high CD4/CD8 groups. Results Compared to the controls, the absolute count of CD3⁺T cells, CD4⁺ T cells, CD3⁺CD25⁺ activated T cells and CD4/CD8 ratio significantly decreased in the peripheral blood of AITL patients at the initial diagnosis. Whereas, the absolute count of CD19⁺ B cells, CD20⁺ B cells, CD5⁺CD19⁺ and CD19⁺CD23⁺ activated B cell significantly decreased. The proportion of CD3⁺ T cells after the first course of chemotherapy significantly increased than that at the initial diagnosis, and the proportion of CD4⁺ T cells, CD3⁺CD25⁺ activated T cells and CD4/CD8 significantly increased after three courses of the treatment. The survival analysis showed that the progression-free-survival (PFS) and overall survival (OS) of the low CD4/CD8 group were significantly higher than those of the CD4/CD8 group. Conclusion High CD4/CD8 ratio in peripheral blood at the initial diagnosis of AITL patients is associated with poor prognosis. CD4⁺ T cell count in the peripheral blood of patients is significantly decreased compared with healthy people, and which can be partially recovered after effective treatment. The analysis on lymphocyte subsets in AITL supports providing new ideas for identifying new prognostic markers of AITL and implementing effective individualized immunotherapy.

Key words: lymphoma, T cells, lymphocyte subsets, CD4⁺ T cells, CD4/CD8

中图分类号:

R733.4

陆洛, 王飞, 顾伟英. 血管免疫母细胞性T细胞淋巴瘤患者外周血淋巴细胞亚群检测的临床意义[J]. 临床荟萃, 2022, 37(11): 1001-1007.

Lu Luo, Wang Fei, Gu Weiying. Clinical determination of lymphocyte subsets in peripheral blood of patients with angioimmunoblastic T cell lymphoma[J]. Clinical Focus, 2022, 37(11): 1001-1007.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.11.007

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I11/1001

图/表 5

表1 两组基本临床特征比较(例)

临床特征	高CD4/CD8组 ( $n$ =5)	低CD4/CD8组 ( $n$ =11)	$P$ 值
年龄
<60岁 ≥60岁	0 5	4 7	0.245
性别
男女	4 1	6 5	0.588
ECOG评分
0~1分 2~4分	1 4	7 4	0.282
Ann Arbor分期
Ⅰ~Ⅱ期 Ⅲ~Ⅳ期	0 5	1 10	1.000
结外
无有	2 3	5 6	1.000
骨髓受累
无有	4 1	10 1	1.000
浆膜腔积液
无有	1 4	6 5	0.308
B症状
无有	2 3	2 9	0.547
LDH
>250 U/L ≤250 U/L	3 2	7 4	1.000
IPI评分
0~2分 3~5分	1 4	4 7	0.622
PIT评分
0~1分 2~4分	0 5	4 7	0.245
PIAI评分
0~1分 2~5分	1 4	1 10	1.000

表1 两组基本临床特征比较(例)

临床特征	高CD4/CD8组 ( $n$ =5)	低CD4/CD8组 ( $n$ =11)	$P$ 值
年龄
<60岁 ≥60岁	0 5	4 7	0.245
性别
男女	4 1	6 5	0.588
ECOG评分
0~1分 2~4分	1 4	7 4	0.282
Ann Arbor分期
Ⅰ~Ⅱ期 Ⅲ~Ⅳ期	0 5	1 10	1.000
结外
无有	2 3	5 6	1.000
骨髓受累
无有	4 1	10 1	1.000
浆膜腔积液
无有	1 4	6 5	0.308
B症状
无有	2 3	2 9	0.547
LDH
>250 U/L ≤250 U/L	3 2	7 4	1.000
IPI评分
0~2分 3~5分	1 4	4 7	0.622
PIT评分
0~1分 2~4分	0 5	4 7	0.245
PIAI评分
0~1分 2~5分	1 4	1 10	1.000

图1 AITL患者诊断时与健康人群淋巴细胞亚群计数的比较 a、b分别为T细胞淋巴亚群及B细胞淋巴亚群

图2 AITL患者治疗前后淋巴细胞亚群的动态变化

图3 CD4/CD8比值对患者PFS及OS的影响

表2 影响AITL患者预后的单因素分析

影响因素	PFS		OS
影响因素	$H R$ (95% $C I$ )	$P$ 值	$H R$ (95% $C I$ )	$P$ 值
年龄	1.048(0.968-1.134)	0.246	1.086(0.092-1.190)	0.076
Ann Arbor分期	3.784(0.537-26.648)	0.181	3.072(0.443-21.320)	0.256
B症状	0.812(0.168-3.938)	0.796	1.065(0.213-5.330)	0.939
ECOG评分	3.408(1.400-8.296)	0.007	3.331(1.256-8.832)	0.016
IPI评分	1.783(0.862-3.685)	0.119	1.487(0.719-3.074)	0.284
PIT评分	4.897(1.510-15.883)	0.008	2.551(0.954-6.822)	0.062
PIAI评分	3.999(1.514-10.562)	0.005	2.185(1.051-4.545)	0.036
结外受累	0.841(0.224-3.154)	0.797	1.193(0.298-4.786)	0.803
骨髓受累	0.915(0.112-7.454)	0.934	0.755(0.092-6.222)	0.794
浆膜腔积液	0.238(0.049-1.158)	0.075	0.103(0.012-0.850)	0.035
Ki67	0.996(0.953-1.040)	0.843	0.990(0.944-1.038)	0.684
LDH	0.999(0.993-1.005)	0.770	1.000(0.993-1.006)	0.880
β₂微球蛋白	1.379(1.037-1.834)	0.027	1.338(0.976-1.834)	0.071
白蛋白	0.773(0.621-0.961)	0.021	0.811(0.654-1.007)	0.058
白细胞	1.059(0.900-1.247)	0.489	1.051(0.883-1.252)	0.576
Kappa链	1.001(1.000-1.003)	0.050	1.002(1.000-1.003)	0.068
Lambda链	1.001(1.000-1.003)	0.036	1.003(1.000-1.006)	0.026
IgG	1.072(0.994-1.156)	0.071	1.102(1.007-1.205)	0.034
CD4/CD8	0.205(0.053-0.792)	0.022	0.136(0.031-0.596)	0.008

表2 影响AITL患者预后的单因素分析

影响因素	PFS		OS
影响因素	$H R$ (95% $C I$ )	$P$ 值	$H R$ (95% $C I$ )	$P$ 值
年龄	1.048(0.968-1.134)	0.246	1.086(0.092-1.190)	0.076
Ann Arbor分期	3.784(0.537-26.648)	0.181	3.072(0.443-21.320)	0.256
B症状	0.812(0.168-3.938)	0.796	1.065(0.213-5.330)	0.939
ECOG评分	3.408(1.400-8.296)	0.007	3.331(1.256-8.832)	0.016
IPI评分	1.783(0.862-3.685)	0.119	1.487(0.719-3.074)	0.284
PIT评分	4.897(1.510-15.883)	0.008	2.551(0.954-6.822)	0.062
PIAI评分	3.999(1.514-10.562)	0.005	2.185(1.051-4.545)	0.036
结外受累	0.841(0.224-3.154)	0.797	1.193(0.298-4.786)	0.803
骨髓受累	0.915(0.112-7.454)	0.934	0.755(0.092-6.222)	0.794
浆膜腔积液	0.238(0.049-1.158)	0.075	0.103(0.012-0.850)	0.035
Ki67	0.996(0.953-1.040)	0.843	0.990(0.944-1.038)	0.684
LDH	0.999(0.993-1.005)	0.770	1.000(0.993-1.006)	0.880
β₂微球蛋白	1.379(1.037-1.834)	0.027	1.338(0.976-1.834)	0.071
白蛋白	0.773(0.621-0.961)	0.021	0.811(0.654-1.007)	0.058
白细胞	1.059(0.900-1.247)	0.489	1.051(0.883-1.252)	0.576
Kappa链	1.001(1.000-1.003)	0.050	1.002(1.000-1.003)	0.068
Lambda链	1.001(1.000-1.003)	0.036	1.003(1.000-1.006)	0.026
IgG	1.072(0.994-1.156)	0.071	1.102(1.007-1.205)	0.034
CD4/CD8	0.205(0.053-0.792)	0.022	0.136(0.031-0.596)	0.008

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