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中国生物工程杂志

China Biotechnology
China Biotechnology  2019, Vol. 39 Issue (9): 50-57    DOI: 10.13523/j.cb.20190907
Orginal Article     
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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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 wordsLymphocyte subsets      Malignant hematological disease      Clinical prognosis     
Received: 12 September 2019      Published: 20 September 2019
ZTFLH:  Q291  
Cite this article:

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.

URL:

https://manu60.magtech.com.cn/biotech/10.13523/j.cb.20190907     OR     https://manu60.magtech.com.cn/biotech/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
Table 1 Changes of lymphoid subsets in patients with malignant hematopathy at different ages
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
Table 2 The percentage of peripheral blood lymphocyte subsets in patients with newly diagnosed malignant hematopathy was compared with that in control group
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
Table 3 The absolute count of peripheral blood lymphocyte subsets in patients with malignant hematopathy was compared with that in control group
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
Table 4 Changes in the proportion of peripheral blood lymphocyte subsets in patients with different malignant hematopathy
Fig.1 Comparison of lymphocyte subsets between AML patients and ALL patients The X-axis represents the type of the lymphocyte subsets, and the Y-axis represents the proportion of the lymphcyte subsets * P<0.05
Fig.2 Lymphocyte subsets were compared between the HL patient group and the NHL patient group The X-axis represents the type of the lymphocyte subsets, and the Y-axis represents the proportion of the lymphocyte subsets * P<0.05
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
Table 5 Comparison of lymphocyte subsets in patients with acute leukemia treated with different initial therapeutic effects
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
Table 6 Comparison of lymphocyte subsets in patients with acute leukemia in the continuous remission group and the relapse group
[1]   Burger J A, Kipps T J . Chemokine receptors and stromal cells in the homing and homeostasis of chronic lymphocytic leukemia B cells. Leukemia & Lymphoma, 2002,43(3):461-466.
[2]   Caligariscappio F . Role of the microenvironment in chronic lymphocytic leukaemia. British Journal of Haematology, 2003,123(3):380-388.
[3]   Swederlow S H, Campo E, Harris N L , et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4 th ed . Lyon: International Agency for Research on Cancer, 2017.
[4]   沈悌, 赵永强 . 血液病诊断及疗效标准.第4版 .北京: 科学出版社, 2018.
[4]   Shen Y, Zhao Y Q. Diagnostic and therapeutic criteria for hematological diseases. 4th edition. Beijing: Science Press, 2018.
[5]   Harris N L, Jaffe E S, Diebold J , et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol, 1999,17(12):3835-3849.
[6]   吴巨峰, 李扬秋, 姚红霞 , 等. 急性白血病患者化疗前后外周血T细胞亚群检测的临床意义. 海南医学, 2011,22(1):4-6.
[6]   Wu J F, Li Y Q, Yao H X , et al. Clinical significance of T lymphocyte subsets in patients with acute leukemia before and after chemotherapy. Hainan Medical Journal, 2011,22(1):4-6.
[7]   Ioannides C G, Whiteside T L . T cell recognition of human tumors: implications for molecular immunotherapy of cancer. Clinical Immunology & Immunopathology, 1993,66(2):91-106.
[8]   Pan P Y, Ozao J, Zhou Z , et al. Advancements in immune tolerance. Advanced Drug Delivery Reviews, 2008,60(2):91-105.
[9]   Piconese S, Colombo M P . Regulatory T cells in cancer. Blood, 2006,108(3):804-811.
[10]   Perreau M, Levy Y, Pantaleo G . Immune response to HIV. Current Opinion in HIV and AIDS, 2013,8(4):333-340.
doi: 10.1097/COH.0b013e328361faf4
[11]   Milosevic, D B . The different level of immunological recovery after chemotherapy in leukemia and lymphoma patients. Journal of Experimental & Clinical Cancer Research, 2001,20(4):517-522.
[12]   薄利魁 . 老年初诊急性髓细胞白血病患者CD4 +CD25 +调节性T细胞的表达 . 中国组织工程研究, 2015,19(1):151-155.
[12]   Bo L K . CD4 +CD25 +Expression of regulatory T cells in aged patients with acute myeloid leukemia. Chinese Journal of Tissue Engineering Research. 2015,19(1):151-155.
[13]   Kelley T W, Parker C J . CD4 (+)CD25 (+)Foxp3 (+) regulatory T cells and hematologic malignancies. Frontiers in Bioscience, 2010,2(1):980-992.
[14]   Chang C, Wu S Y, Kang Y W , et al. High levels of regulatory T cells in blood are a poor prognostic factor in patients with diffuse large B-cell lymphoma. Am J Clin Pathol, 2015,144(6):935-944.
[15]   Sofia K, Margarita B, Despina B , et al. Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL. Pediatric Blood & Cancer, 2010,50(3):528-532.
[16]   郑润辉, 于宝丹, 郑丽霞 , 等. 急性白血病患者T细胞亚群的变化及其与临床特征和预后的关系. 中国实验血液学杂志, 2018,26(5):1309-1316.
[16]   Zheng R H, Yu B D, Zheng L X , et al. Changes of T cell subsets and their relationship with clinical features and prognosis in patients with acute leukemia. Journal of Experimental Hematology, 2018,26(5):1309-1316.
[17]   喻霞云, 顾国浩, 王琳 , 等. 外周血淋巴细胞亚群绝对值精确定量分析急性白血病的免疫功能. 中国现代医学杂志, 2014,24(17):63-67.
[17]   Yu X Y, Gu G H, Wang L , et al. Peripheral blood lymphocyte subsets of the absolute value of precise and quantitative analysis of immune function in acute leukemia. China Journal of Modern Medicine, 2014,24(17):63-67.
[18]   Plonquet A, Haioun C J, Debard A , et al. Peripheral blood natural killer cell count is associated with clinical outcome in patients with aaIPI 2-3 diffuse large B-cell lymphoma. Annals of Oncology, 2007,18(7):1209-1215.
[19]   甄敬飞, 包芳, 朱明霞 , 等. 外周血免疫细胞亚群的变化与B细胞淋巴瘤患者的预后关系研究. 中国实验血液学杂志, 2018,26(6):87-92.
[19]   Zhen J F, Bao F, Zhu M X , et al. Relationship of the changes of peripheral blood immuno-cell subsets with the prognosis of B cell lymphoma patients. Journal of Experimental Hematology, 2018,26(6):87-92.
[20]   Deepti B, Kay R, Markovic S N , et al. Absolute lymphocyte count predicts therapeutic efficacy of rituximab therapy in follicular lymphomas. British Journal of Haematology, 2010,137(5):409-415.
[21]   Shafer D, Smith M R, Borghaei H , et al. Low NK cell counts in peripheral blood are associated with inferior overall survival in patients with follicular lymphoma. Leukemia Research, 2013,37(10):1213-1215.
doi: 10.1016/j.leukres.2013.07.038
[22]   Curiel T J, Coukos G L, Alvarez X , et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nature Medicine, 2004,10(9):942-949.
[23]   Griffiths R W, Elkord E, Gilham D E , et al. Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunology Immunotherapy, 2007,56(11):1743-1753.
doi: 10.1007/s00262-007-0318-z
[24]   Wang X, Zheng J, Liu J , et al. Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients. European Journal of Haematology, 2010,75(6):468-476.
[25]   路萍, 侯十前, 王永志 , 等. 白血病患者化疗前后调节性T细胞的表达与微小残留白血病的关系. 昆明医科大学学报, 2015,36(4):93-96.
[25]   Lu P, Hou S Q, Wang Y Z , et al. Correlation between regulatory T cell express and minimal residual leukemia before and after chemotherapy. Journal of Kunming Medical University, 2015,36(4):93-96.
[26]   Szczepanski M J, Marta S, Malgorzata C , et al. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clinical Cancer Research, 2009,15(10):3325-3332.
[27]   张司琪, 葛健, 夏瑞祥 . 急性白血病患者外周血T细胞亚群、NK细胞和调节性T细胞的检测及临床意义. 安徽医科大学学报, 2016,51(2):218-221.
[27]   Zhang S Q, Ge J, Xia R X . Detection of T lymphocyte subsets,NK cells,regulatory T cells in peripheral blood of patients with acute leukemia and its clinical significance. Acta Universitatis Medicinalis Anhui, 2016,51(2):218-221.
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