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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2019, Vol. 39 Issue (9): 50-57    DOI: 10.13523/j.cb.20190907
研究报告     
恶性血液病患者外周血淋巴细胞亚群变化及其临床意义的研究
冉隆荣,薛宁,王建容,杜英剑,毛金菊,周泉佑,杨再林()
重庆医科大学附属第三医院(捷尔医院) 重庆 401120
Prognostic Significance of Peripheral Blood Lymphocyte Subsets in Patients with Hematologic Malignancies
RAN Long-rong,XUE Ning,WANG Jian-rong,DU Ying-jian,MAO Jin-ju,ZHOU Quan-you YANG Zai-lin
Department of Laboratory Medicine, The Third Affiliated Hospital of Chongqing Medical University(Gener Hospital), Chongqing 401120, China
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摘要：

目的: 探讨恶性血液病外周血淋巴细胞亚群变化特征及临床意义。方法: 采用流式细胞仪检测64例初诊的血液系统恶性肿瘤患者的外周血淋巴细胞亚群。病种包括急性髓系白血病(acute myeloid leukemia,AML)、急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)、霍奇金淋巴瘤(Hodgkin’s lymphoma,HL)、非霍奇金淋巴瘤(Non-Hodgkinlymphoma,NHL)。分析比较30例正常人的外周血淋巴细胞亚群与实验组的差异,并对64例恶性血液病患者中连续动态监测的21例急性白血病患者外周血淋巴细胞亚群结果变化与预后关系进行分析。结果： 不同成人恶性血液病患者年龄分组淋巴细胞亚群变化无明显差异;恶性血液病患者中CD3 +CD8 + T淋巴细胞百分比、Treg细胞百分比均增加;CD16 +/CD56 +NK细胞百分比及CD4 +/CD8 +比值均下降;CD3 +T淋巴细胞数量、CD3 +CD4 +淋巴细胞数、CD3 +CD8 +淋巴细胞数量、CD3 -CD19 +淋巴细胞数量、CD16 +/CD56 +NK淋巴细胞数量及CD4 +/CD8 +比值均减少;急性白血病及恶性淋巴瘤患者外周血淋巴细胞亚群与正常对照组比较存在一定的差异;急性白血病未缓解组的Treg细胞比例明显高于急性白血病首疗程缓解组及对照组;急性白血病复发组Treg细胞比例明显高于急性白血病持续缓解组以及对照组;对21例急性白血病患者动态监测的淋巴细胞亚群发现,化疗缓解的患者Treg在化疗过程中逐渐下降,至第3~6个疗程逐渐接近正常对照,化疗未缓解的患者Treg细胞在化疗过程中逐渐上升或持续大于10%,明显高于完全缓解组,复发患者Treg在化疗过程中先下降后明显上升。 结论： 恶性血液病患者免疫功能显著低于健康人,且伴随免疫功能紊乱,且不同疾病类型、不同的疾病状态免疫紊乱的程度不一,Treg细胞比例可以用来预测急性白血病患者疗效及复发,可以为患者的临床治疗方案及用药强度提供指导依据。
关键词： 淋巴细胞亚群;  恶性血液病;  临床预后    
Abstract:

Objective: To investigate the effect of peripheral blood lymphocyte subsets and clinical characteristics on the prognosis of hematologic malignancies.Methods: The peripheral blood lymphocyte subsets of 64 patients with newly diagnosed hematologic malignancy were detected by flow cytometry. Diseases included Acute myeloid leukemia (AML)、Acute lymphoblastic leukemia (ALL)、Hodgkin’s lymphoma (HL)、non-Hodgkin’s lymphoma as bone marrow infiltration (NHL). We analyzed the difference of peripheral blood lymphocyte subsets between 30 normal patients and the experimental group. And We analyzed the relationship between the changes of peripheral blood lymphocyte subsets and prognosis in 21 patients with acute leukemia who underwent continuous dynamic monitoring in 64 patients with malignant hematological diseases.Results: No significant difference was shown in lymphocyte subsets among different age groups of adult patients with malignant hematopathy. The percentage of CD3 +CD8 + T lymphocytes and T-reg cells in patients with malignant hematopathy increased, while the percentages of CD16 +/CD56 +NK cells, and CD4 +/CD8 + ratio were all decreased. The number of CD3 +T lymphocyte, CD3 +CD4 + lymphocyte, CD3 +CD8 + lymphocyte, CD19 + lymphocytes, CD16 +/CD56 + lymphocyte and CD4 +/CD8 + ratio were all decreased. There were some differences in peripheral blood lymphocyte subsets between acute leukemia and malignant lymphoma patients and control group. The proportion of T-reg cells in non-remission group of acute leukemia was significantly higher than that in remission group of first course of treatment of acute leukemia and control group. The proportion of T-reg cells in relapsed acute leukemia group was remarkably higher than that in sustained remission group and control group. In 21 patients with acute leukemia, we found that T-reg cells in remission group gradually decreased during chemotherapy and gradually approached the control group during the third to sixth courses of treatment. T-reg cells in non-remission group increased gradually or continued to exceed 10% in the course of chemotherapy, which was significantly higher than remission group. Furthermore, T-reg cells shown a trend of first subtraction and then addition during the chemotherapy in recurrence patients. Conclusion: The immune function of patients with malignant hematological diseases is significantly lower than that of healthy people, and accompanied by immune dysfunction. In addition, different types of diseases and different disease states brought about different degrees of immune disorders.the proportion of T-reg cells can be used to predict the curative effect and recurrence in patients with hematologic malignancies, for providing guidance basis for clinical treatment and medication intensity.

Key words: Lymphocyte subsets    Malignant hematological disease    Clinical prognosis
收稿日期: 2019-09-12 出版日期: 2019-09-20
ZTFLH:  Q291  
通讯作者: 杨再林     E-mail: 651086@hospital.cqmu.edu.cn
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引用本文:

冉隆荣,薛宁,王建容,杜英剑,毛金菊,周泉佑,杨再林. 恶性血液病患者外周血淋巴细胞亚群变化及其临床意义的研究[J]. 中国生物工程杂志, 2019, 39(9): 50-57.

RAN Long-rong,XUE Ning,WANG Jian-rong,DU Ying-jian,MAO Jin-ju,ZHOU Quan-you YANG Zai-lin. Prognostic Significance of Peripheral Blood Lymphocyte Subsets in Patients with Hematologic Malignancies. China Biotechnology, 2019, 39(9): 50-57.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190907    或    https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I9/50

年龄 CD3(%) CD4(%) CD8(%) CD4/CD8 Treg(%) CD19(%) CD16+56(%)
≥60岁 70.90±8.67 35.21±14.96 34.21±14.92 1.05±0.63 8.76±4.25 12.47±5.74 12.45±9.02
<60岁 71.12±9.02 34.78±13.65 35.21±15.36 0.97±0.45 8.31±5.36 13.13±5.24 12.97±7.69
表1  不同年龄恶性血液病患者淋巴亚群水平的变化(%,x±s,n=64)
分组 CD3(%) CD4(%) CD8(%) CD4/CD8 Treg(%) CD19(%) CD16+56(%)
患者组 70.12±10.68 34.12±13.78 34.36±15.87* 1.02±0.68* 8.51±2.17* 13.63±4.31 12.64±5.01*
对照组 71.67±7.64 37.54±6.13 26.71±6.71 1.54±0.67 6.76±2.01 12.26±4.10 15.37±4.40
表2  初诊恶性血液病患者外周血淋巴细胞亚群百分比与正常对照比较(%,x±s,n=64)
分组 CD3 CD4 CD8 CD19 CD16+56
患者组 779.65±413.53* 389.83±228.13* 361.26±192.16* 88.76±39.47* 187.63±92.47*
对照组 1239.10±314.56 656.09±207.90 452.89±157.69 219.03±113.12 252.76±129.75
表3  恶性血液病患者的外周血淋巴细胞亚群的绝对数与正常对照相比较(×106/L,x±s,n=64)
分组 n CD3(%) CD4(%) CD8(%) CD4/CD8 Treg(%) CD19(%) CD16+56(%)
AML 28 68.01±18.79 34.62±4.95 31.24±7.58* 1.09±0.51* 9.23±3.33* 12.34±7.17 14.58±7.10
ALL 15 67.62±21.34 26.84±6.56* 38.42±10.69* 0.87±0.46* 9.62±4.45* 14.45±7.86 6.31±4.51*
HL 6 72.45±14.87 31.25±11.65* 33.25±8.61* 1.02±0.59* 7.36±4.30 12.61±3.53 13.36±4.60
NHL 15 71.36±16.54 30.69±12.46* 41.36±13.65* 0.78±0.62* 7.56±4.62 14.35±3.63 16.71±4.29
对照组 30 71.67±7.64 37.54±6.13 26.71±6.71 1.54±0.67 6.76±2.01 12.26±4.10 15.37±4.40
表4  不同恶性血液病患者外周血淋巴细胞亚群比例变化(%,x±s)
图1  AML患者组与ALL患者组淋巴细胞亚群比较
图2  HL患者组与NHL患者组比较淋巴细胞亚群比较
分组 n CD3(%) CD4(%) CD8(%) CD4/CD8 Treg(%) CD19(%) CD16+56(%)
首缓解组 22 71.72±11.65 36.46±13.29 33.43±5.83 1.20±0.58 7.06±2.96 11.68±6.01 15.67±6.31
未缓解组 13 69.23±12.30 34.62±15.27 31.89±8.56 1.12±0.74 9.37±2.81*# 13.12±5.39 14.36±5.68
对照组 30 71.67±7.64 37.54±6.13 26.71±6.71 1.54±0.67 6.76±2.01 12.26±4.10 15.37±4.40
表5  急性白血病首疗程疗效不同组的淋巴亚群对比(%,x±s)
分组 n CD3(%) CD4(%) CD8(%) CD4/CD8 Treg(%) CD19(%) CD16+56(%)
持续缓解组 19 69.27±11.59 35.21±9.87 28.67±5.01 1.33±0.56 7.19±2.24 12.08±4.28 15.67±4.60
复发组 5 68.69±14.17 34.36±11.26 29.35±7.89 1.19±0.81 9.56±2.31*# 11.56±3.84 14.39±5.61
对照组 30 71.67±7.64 37.54±6.13 26.71±6.71 1.54±0.67 6.76±2.01 12.26±4.10 15.37±4.40
表6  急性白血病持续缓解组及复发组的淋巴亚群与对比(%,x±s)
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