弥漫大B细胞淋巴瘤是最常见的非霍奇金淋巴瘤,具有高度异质性。利妥昔单抗时代,患者的治愈率得到很大的提高,但仍有部分患者出现耐药或早期复发,传统的预后评估手段在新时期受到了极大的挑战。近些年,血清标志物因其易获得、便于动态评估和价格低廉等优势,在DLBCL的预后评估中的作用受到关注。本文就初诊及治疗过程中患者的外周血淋巴细胞/单核细胞比值(LMR)、β2微球蛋白(β2MG)、红细胞沉降率(ESR)、红细胞分布宽度(RDW)做一综述。
Diffuse large B-cell lymphoma is the most common non-Hodgkin lymphoma and is highly heteroge-neous. In the era of rituximab, the cure rate of patients has been greatly improved, but some pa-tients still develop drug resistance or early recurrence, and the traditional prognostic evaluation methods have been greatly challenged in the new period. In recent years, the role of serum markers in the prognosis assessment of DLBCL has attracted attention because of its advantages of easy availability, easy dynamic assessment and low price. In this paper, the peripheral blood lympho-cyte/monocyte ratio (LMR), β2 microglobulin (β2MG), erythrocyte sedimentation rate (ESR), and red blood cell distribution width (RDW) of patients during initial diagnosis and treatment are reviewed.
弥漫大B细胞淋巴瘤,血清标志物,预后, Diffuse Large B-Cell Lymphoma Serum Markers Prognosis摘要
Diffuse large B-cell lymphoma is the most common non-Hodgkin lymphoma and is highly heterogeneous. In the era of rituximab, the cure rate of patients has been greatly improved, but some patients still develop drug resistance or early recurrence, and the traditional prognostic evaluation methods have been greatly challenged in the new period. In recent years, the role of serum markers in the prognosis assessment of DLBCL has attracted attention because of its advantages of easy availability, easy dynamic assessment and low price. In this paper, the peripheral blood lymphocyte/monocyte ratio (LMR), β2 microglobulin (β2MG), erythrocyte sedimentation rate (ESR), and red blood cell distribution width (RDW) of patients during initial diagnosis and treatment are reviewed.
Keywords:Diffuse Large B-Cell Lymphoma, Serum Markers, Prognosis
付 滕,杨香会,张海亚,王彦丽,李 丽,接贵涛. 血清标志物与弥漫大B细胞淋巴瘤预后关系的研究进展Research Advances in the Relationship between Serum Markers and the Prognosis of Diffuse Large B-Cell Lymphoma[J]. 临床医学进展, 2022, 12(07): 6239-6245. https://doi.org/10.12677/ACM.2022.127901
参考文献ReferencesLi, S., Young, K.H. and Medeiros, L.J. (2018) Diffuse Large B-Cell Lymphoma. Pathology, 50, 74-87.
<br>https://doi.org/10.1016/j.pathol.2017.09.006Jamil, M.O. and Mehta, A. (2016) Diffuse Large B-Cell Lym-phoma: Prognostic Markers and Their Impact on Therapy. Expert Review of Hematology, 9, 471-477. <br>https://doi.org/10.1586/17474086.2016.1146584Cunningham, D., Hawkes, E.A., Jack, A., et al. (2013) Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone in Patients with Newly Diagnosed Dif-fuse Large B-Cell Non-Hodgkin Lymphoma: A Phase 3 Comparison of Dose Intensification with 14-Day versus 21-Day Cycles. Lancet, 381, 1817-1826.
<br>https://doi.org/10.1016/S0140-6736(13)60313-XIwahori, K., Shintani, Y., Funaki, S., et al. (2019) Peripher-al T Cell Cytotoxicity Predicts T Cell Function in the Tumor Microenvironment. Scientific Reports, 9, Article No. 2636. <br>https://doi.org/10.1038/s41598-019-39345-5杨迪, 苏丽萍. 外周血淋巴细胞/单核细胞比值(LMR)及其与乳酸脱氢酶比值对弥漫大B细胞淋巴瘤患者预后的影响[J]. 中国实验血液学杂志, 2020, 28(5): 1563-1569.Mohsen, A., Taalab, M., Abousamra, N. and Mabed, M. (2020) Prognostic Significance of Absolute Lymphocyte Count, Absolute Monocyte Count, and Absolute Lymphocyte Count to Absolute Monocyte Count Ratio in Follicular Non-Hodgkin Lymphoma. Clinical Lymphoma, Myeloma and Leukemia, 20, e606-e615.
<br>https://doi.org/10.1016/j.clml.2020.03.007Sawa-Wejksza, K. and Kandefer-Szerszeń, M. (2018) Tu-mor-Associated Macrophages as Target for Antitumor Therapy. Archivum Immunologiae et Therapiae Experimentalis (Warsz), 66, 97-111.
<br>https://doi.org/10.1007/s00005-017-0480-8刘琦, 郭鹏, 詹文华. LMR和LMR/LDH对原发韦氏环弥漫大B 细胞淋巴瘤预后的影响[J]. 肿瘤防治研究, 2022, 49(2): 110-115.黄鑫, 岑洪. 外周血炎症指标与弥漫大B细胞淋巴瘤预后关系的研究进展[J]. 中国癌症防治杂志, 2019, 11(6): 536-540.Rusak, M., Bołkun, Ł., Chociej-Stypułkowska, J., Pawlus, J., Kłoczko, J. and Dąbrowska, M. (2016) Flow-Cytometry- Based Evaluation of Pe-ripheral Blood Lymphocytes in Prognostication of Newly Diagnosed DLBCL Patients. Blood Cells, Molecules, and Diseases, 59, 92-96. <br>https://doi.org/10.1016/j.bcmd.2016.04.004蔡春颖, 孙丽霞, 吕鸿雁. 初诊时非霍奇金淋巴瘤患者外周血淋巴细胞与单核细胞比值在预后评估中的作用[J]. 临床荟萃, 2016, 31(7): 736-740.Bento, L., Díaz-López, A., Barranco, G., et al. (2020) New Prognosis Score Including Absolute Lym-phocyte/Monocyte Ratio, Red Blood Cell Distribution Width and Beta-2 Microglobulin in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Spanish Lymphoma Group Experience (GELTAMO). British Journal of Haematology, 188, 888-897. <br>https://doi.org/10.1111/bjh.16263Zhou, S., Xu, L., Ma, Y., et al. (2017) Pe-ripheral Blood Lymphocyte to Monocyte Ratio Recovery from Low Levels at Diagnosis after Completion of First Line Therapy Predicts Good Clinical Outcomes in Patients with Diffuse Large B-Cell Lymphoma. Oncotarget, 8, 19556-19565. <br>https://doi.org/10.18632/oncotarget.14700Belotti, A., Doni, E., Bolis, S., et al. (2015) Periph-eral Blood Lymphocyte/Monocyte Ratio Predicts Outcome in Follicular Lymphoma and in Diffuse Large B-Cell Lym-phoma Patients in the Rituximab Era. Clinical Lymphoma, Myeloma and Leukemia, 15, 208-213. <br>https://doi.org/10.1016/j.clml.2014.10.001Porrata, L.F., Ristow, K.M., Habermann, T.M., et al. (2014) Pe-ripheral Blood Absolute Lymphocyte/Monocyte Ratio during Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone Treatment Cycles Predicts Clinical Outcomes in Diffuse Large B-Cell Lymphoma. Leukemia & Lym-phoma, 55, 2728-2738.
<br>https://doi.org/10.3109/10428194.2014.893313Grey, H.M., Kubo, R.T., Colon, S.M., et al. (1973) The Small Subunit of HL-A Antigens Is Beta 2-Microglobulin. Journal of Experimental Medicine, 138, 1608-1612. <br>https://doi.org/10.1084/jem.138.6.1608Peterson, P.A., Cunningham, B.A., Berggård, I. and Edelman, G.M. (1972) 2-Microglobulin—A Free Immunoglobulin Domain. Proceedings of the National Academy of Sciences of the United States of America, 69, 1697-1701.
<br>https://doi.org/10.1073/pnas.69.7.1697Shi, C., Zhu, Y., Su, Y., Chung, L.W. and Cheng, T. (2009) Be-ta2-Microglobulin: Emerging as a Promising Cancer Therapeutic Target. Drug Discovery Today, 14, 25-30. <br>https://doi.org/10.1016/j.drudis.2008.11.001Muñana, K.R., Saito, M. and Hoshi, F. (2007) Be-ta-2-Microglobulin Levels in the Cerebrospinal Fluid of Normal Dogs and Dogs with Neurological Disease. Veterinary Clinical Pathology, 36, 173-178.
<br>https://doi.org/10.1111/j.1939-165X.2007.tb00204.xSvatoňová, J., Bořecká, K., Adam, P. and Lánská, V. (2014) Beta2-Microglobulin as a Diagnostic Marker in Cerebrospinal Fluid: A Follow-Up Study. Disease Markers, 2014, Article ID: 495402. <br>https://doi.org/10.1155/2014/495402Huang, W.C., Wu, D., Xie, Z., et al. (2006) Beta2-Microglobulin Is a Signaling and Growth-Promoting Factor for Human Prostate Cancer Bone Metastasis. Cancer Research, 66, 9108-9116.Berggård, I. and Bearn, A.G. (1968) Isolation and Properties of a Low Molecular Weight Beta-2-Globulin Occurring in Human Biological Fluids. Journal of Biological Chemistry, 243, 4095-4103.
<br>https://doi.org/10.1016/S0021-9258(18)93284-9Kanemasa, Y., Shimoyama, T., Sasaki, Y., et al. (2017) Be-ta-2 Microglobulin as a Significant Prognostic Factor and a New Risk Model for Patients with Diffuse Large B-Cell Lymphoma. Hematological Oncology, 35, 440-446.
<br>https://doi.org/10.1002/hon.2312Federico, M., Bellei, M., Marcheselli, L., et al. (2009) Follicular Lymphoma International Prognostic Index 2: A New Prognostic Index for Follicular Lymphoma Developed by the International Fol-licular Lymphoma Prognostic Factor Project. Journal of Clinical Oncology, 27, 4555-4562. <br>https://doi.org/10.1200/JCO.2008.21.3991Chen, Y., Neelapu, S., Feng, L., et al. (2016) Prognostic Signifi-cance of Baseline Peripheral Absolute Neutrophil, Monocyte and Serum β2-Microglobulin Level in Patients with Diffuse Large B-Cell Lymphoma: A New Prognostic Model. British Journal of Haematology, 175, 290-299. <br>https://doi.org/10.1111/bjh.14237Wu, S., Zhou, Y., Hua, H.Y., et al. (2018) Inflammation Marker ESR Is Effective in Predicting Outcome of Diffuse Large B-Cell Lymphoma. BMC Cancer, 18, Article No. 997. <br>https://doi.org/10.1186/s12885-018-4914-4Strojnik, T., Smigoc, T. and Lah, T.T. (2014) Prognostic Value of Erythrocyte Sedimentation Rate and C-Reactive Protein in the Blood of Patients with Glioma. Anticancer Research, 34, 339-347.章尤权, 沈冬祎, 吕嘉婧, 等. 弥漫大B细胞淋巴瘤患者血浆红细胞沉降率与预后的相关性研究[J]. 福建医药杂志, 2021, 43(6): 21-25.Go, D.J., Lee, E.Y., Lee, E.B., Song, Y.W., Konig, M.F. and Park, J.K. (2016) Elevated Erythrocyte Sedimentation Rate Is Predictive of Interstitial Lung Disease and Mortality in Dermatomyo-sitis: A Korean Retrospective Cohort Study. Journal of Korean Medical Science, 31, 389-396. <br>https://doi.org/10.3346/jkms.2016.31.3.389Rotaru, I., Găman, G.D., Stănescu, C. and Găman, A.M. (2014) Evaluation of Parameters with Potential Prognosis Impact in Patients with Primary Gastric Diffuse Large B-Cell Lym-phoma (PG-DLBCL). Romanian Journal of Morphology and Embryology, 55, 15-21.Salvagno, G.L., Sanchis-Gomar, F., Picanza, A. and Lippi, G. (2015) Red Blood Cell Distribution Width: A Simple Parameter with Mul-tiple Clinical Applications. Critical Reviews in Clinical Laboratory Sciences, 52, 86-105.
<br>https://doi.org/10.3109/10408363.2014.992064Förhécz, Z., Gombos, T., Borgulya, G., Pozsonyi, Z., Prohá-szka, Z. and Jánoskuti, L. (2009) Red Cell Distribution Width in Heart Failure: Prediction of Clinical Events and Rela-tionship with Markers of Ineffective Erythropoiesis, Inflammation, Renal Function, and Nutritional State. American Heart Journal, 158, 659-666.
<br>https://doi.org/10.1016/j.ahj.2009.07.024Lippi, G., Targher, G., Montagnana, M., Salvagno, G.L., Zoppini, G. and Guidi, G.C. (2009) Relation between Red Blood Cell Distribution Width and Inflammatory Biomarkers in a Large Cohort of Unselected Outpatients. Archives of Pathology & Laboratory Medicine, 133, 628-632. <br>https://doi.org/10.5858/133.4.628Nemeth, E. and Ganz, T. (2014) Anemia of Inflammation. Hematolo-gy/Oncology Clinics of North America, 28, 671-681.
<br>https://doi.org/10.1016/j.hoc.2014.04.005Singh, R., Mishra, M.K. and Aggarwal, H. (2017) Inflammation, Immunity, and Cancer. Mediators of Inflammation, 2017, Article ID: 6027305. <br>https://doi.org/10.1155/2017/6027305Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
<br>https://doi.org/10.1016/j.cell.2011.02.013Goyal, H., Gupta, S. and Singla, U. (2016) Level of Red Cell Dis-tribution Width Is Affected by Various Factors. Clinical Chemistry and Laboratory Medicine, 54, e387. <br>https://doi.org/10.1515/cclm-2016-0195Qin, Y.Y., Wu, Y.Y., Xian, X.Y., et al. (2018) Single and Combined Use of Red Cell Distribution Width, Mean Platelet Volume, and Cancer Antigen 125 for Differential Diagnosis of Ovar-ian Cancer and Benign Ovarian Tumors. Journal of Ovarian Research, 11, 10. <br>https://doi.org/10.1186/s13048-018-0382-3Cheng, S., Han, F., Wang, Y., et al. (2017) The Red Distribution Width and the Platelet Distribution Width as Prognostic Predictors in Gastric Cancer. BMC Gastroenterology, 17, Article No. 163.
<br>https://doi.org/10.1186/s12876-017-0685-7Sun, P., Zhang, F., Chen, C., et al. (2016) The Ratio of Hemo-globin to Red Cell Distribution Width as a Novel Prognostic Parameter in Esophageal Squamous Cell Carcinoma: A Ret-rospective Study from Southern China. Oncotarget, 7, 42650-42660. <br>https://doi.org/10.18632/oncotarget.9516Han, F., Shang, X., Wan, F., et al. (2018) Clinical Value of the Preoperative Neutrophil-to-Lymphocyte Ratio and Red Blood Cell Distribution Width in Patients with Colorectal Carci-noma. Oncology Letters, 15, 3339-3349.
<br>https://doi.org/10.3892/ol.2017.7697Howell, J., Pinato, D.J., Ramaswami, R., et al. (2017) Integration of the Cancer-Related Inflammatory Response as a Stratifying Biomarker of Survival in Hepatocellular Carcinoma Treated with Sorafenib. Oncotarget, 8, 36161-36170.
<br>https://doi.org/10.18632/oncotarget.15322Ichinose, J., Murakawa, T., Kawashima, M., et al. (2016) Prog-nostic Significance of Red Cell Distribution Width in Elderly Patients Undergoing Resection for Non-Small Cell Lung Cancer. Journal of Thoracic Disease, 8, 3658-3666.
<br>https://doi.org/10.21037/jtd.2016.12.44Wang, J., Xie, X., Cheng, F., et al. (2017) Evaluation of Pretreatment Red Cell Distribution Width in Patients with Multiple Myeloma. Cancer Biomarkers, 20, 267-272. <br>https://doi.org/10.3233/CBM-170032Zhou, S., Fang, F., Chen, H., et al. (2017) Prognostic Significance of the Red Blood Cell Distribution Width in Diffuse Large B-Cell Lymphoma Patients. Oncotarget, 8, 40724-40731. <br>https://doi.org/10.18632/oncotarget.16560Periša, V., Zibar, L., Sinčić-Petričević, J., Knezović, A., Periša, I. and Barbić, J. (2015) Red Blood Cell Distribution Width as a Simple Negative Prognostic Factor in Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Study. Croatian Medical Journal, 56, 334-343. <br>https://doi.org/10.3325/cmj.2015.56.334Li, M., Xia, H., Zheng, H., et al. (2019) Red Blood Cell Distribution Width and Platelet Counts Are Independent Prognostic Factors and Improve The Predictive Ability of IPI Score in Dif-fuse Large B-Cell Lymphoma Patients. BMC Cancer, 19, Article No. 1084. <br>https://doi.org/10.1186/s12885-019-6281-1