淋巴瘤相关噬血细胞综合征的诊疗进展
Progress in Diagnosis and Treatment of Lymphoma-Associated Hemophagocytic Syndrome
DOI: 10.12677/acm.2024.1441174, PDF,   
作者: 张涵越, 周 慷*:重庆医科大学附属第二医院血液科,重庆
关键词: 噬血细胞综合征淋巴瘤诊断治疗Hemophagocytic Syndrome Lymphoma Diagnosis Treatment
摘要: 噬血细胞综合征(Hemophagocytic Syndrome, HPS)又称噬血细胞性淋巴组织细胞增多症(Hemphagocytic Lymphohistiocytosis, HLH)是一种由于原发性或继发性免疫异常导致的一类罕见但致命的过度炎症反应综合征,主要症状包括长期发热、血细胞减少、肝脾肿大。淋巴瘤相关噬血细胞综合征(Lymphoma Associated Hemophagocytic Syndrome, LAHS)患者多数病情危重、误诊率、延诊率和死亡率较高,本文就LAHS诊断及治疗等方面进行综述,旨在提高对LAHS的认识,指导临床治疗。
Abstract: Hemophagocytic syndrome (HPS), also known as hemophagocytic lymphohistiocytosis (HLH), is a rare but fatal excessive inflammatory response syndrome caused by primary or secondary immune abnormalities. The main symptoms include long-term fever, cytopenia and hepatosplenomegaly. Most patients with lymphoma-associated hemophagocytic syndrome (LAHS) are in critical condition, with high misdiagnosis rate, delayed diagnosis rate and mortality rate, this article reviews the diagnosis and treatment of LAHS in order to improve the understanding of LAHS and guide clinical treatment.
文章引用:张涵越, 周慷. 淋巴瘤相关噬血细胞综合征的诊疗进展[J]. 临床医学进展, 2024, 14(4): 1402-1408. https://doi.org/10.12677/acm.2024.1441174

参考文献

[1] Farquhar, J.W. and Claireaux, A.E. (1952) Familial Haemophagocytic Reticulosis. Archives of Disease in Childhood, 27, 519-525. [Google Scholar] [CrossRef] [PubMed]
[2] Ishii, E. (2016) Hemophagocytic Lymphohistiocytosis in Children: Pathogenesis and Treatment. Frontiers in Pediatrics, 4, Article 202648. [Google Scholar] [CrossRef] [PubMed]
[3] Yao, S., Wang, Y., Sun, Y., et al. (2021) Epidemiological Investigation of Hemophagocytic Lymphohistiocytosis in China. Orphanet Journal of Rare Diseases, 16, Article No. 342. [Google Scholar] [CrossRef] [PubMed]
[4] Chang, Y., Cui, M., Fu, X., et al. (2018) Lymphoma Associated Hemophagocytic Syndrome: Asingle-Center Retrospective Study. Oncology Letters, 16, 1275-1284. [Google Scholar] [CrossRef] [PubMed]
[5] Li, B., Guo, J., Li, T., et al. (2021) Clinical Characteristics of Hemophagocytic Lymphohistiocytosis Associated with Non-Hodgkin B-Cell Lymphoma: A Multicenter Retrospective Study. Clinical Lymphoma, Myeloma and Leukemia, 21, E198-E205. [Google Scholar] [CrossRef
[6] Henter, J.I., Horne, A., Aric6, M., et al. (2007) HL-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis. Pediatric Blood & Cancer, 48, 124-131. [Google Scholar] [CrossRef] [PubMed]
[7] 王昭, 石远凯. 淋巴瘤相关噬血细胞综合征诊治中国专家共识(2022年版) [J]. 中华医学杂志, 2022, 102(24): 1794-1801.
[8] Xie, M., Li, L., Zhu, L., et al. (2018) An Effective Diagnostic Index for Lymphoma-Associated Hemophagocytic Syndrome. QJM: An International Journal of Medicine, 111, 541-547. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, C.L., Li, M.J., Liu, Y.N., et al.(2019) Expression and Its Implications of Th1/Th2 Cytokines and Lymphocyte Subsets in Adult Patients with Lymphoma-Associated Hemophagocytic Lymphohistiocytosis. Chinese Journal of Hematology, 40, 777-779.
[10] 张文丽, 许蕾, 张倩, 等. 流式细胞分析对以噬血细胞综合征为首发症状的非霍奇金淋巴瘤的诊断价值分析[J]. 中华内科杂志, 2020, 59(12): 976-981.
[11] Yuan, S., Wang, Y., Luo, H., et al. (2020) Serum Soluble VSIG4 as a Surrogate Marker for the Diagnosis of Lymphoma-Associated Hemophagocytic Lymphohistiocytosis. British Journal of Haematology, 189, 72-83. [Google Scholar] [CrossRef] [PubMed]
[12] Hayden, A., Lin, M., Park, S., et al. (2017) Soluble Interleukin-2 Receptor Is a Sensitive Diagnostic Test in Adult HLH. Blood Advances, 1, 2529-2534. [Google Scholar] [CrossRef] [PubMed]
[13] Zoref-Lorenz, A., Murakami, J., Hofstetter, L., et al. (2022) An Improved Index for Diagnosis and Mortality Prediction in Malignancy-Associated Hemophagocytic Lymphohistiocytosis. Blood, 139, 1098-1110. [Google Scholar] [CrossRef] [PubMed]
[14] Zou, H., He, L., Hue, Z., et al. (2023) Serum SCD25/Ferritin Ratio Combined with MCP-1 Is a Valid Predictor for Identifying LAHS with HLH as the First Manifestation. Journal of Cancer Research and Clinical Oncology, 149, 8521-8533. [Google Scholar] [CrossRef] [PubMed]
[15] Ren, Q., Chan, K.W., Huang, H., et al. (2020) Platelet-Derived α-Granules Are Associated with Inflammation in Patients with NK/T-Cell Lymphoma-Associated Hemophagocytic Syndrome. Cytokine, 126, Article ID: 154878. [Google Scholar] [CrossRef] [PubMed]
[16] He, Y.X., Gao, Y., Wang, X., et al. (2023) The Lymphocyte Subsets Activation Profiles in Peripheral Blood May Contribute to the Diagnosis of Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis. Blood, 142, 6218. [Google Scholar] [CrossRef
[17] Lin, C.H., Shih, Y.H., Chen, T.C., et al. (2021) A Decade of Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: Does the Outcome Improve? Journal of Clinical Medicine, 10, Article 5114. [Google Scholar] [CrossRef] [PubMed]
[18] Li, N., Jiang, M., Wu, W.C., et al. (2022) Lymphoma-Associated Hemophagocytic Syndrome: A Retrospective Study from a Single Center. Hematology, 27, 909-916. [Google Scholar] [CrossRef] [PubMed]
[19] 郑良达, 江文华,王娴婷, 等. P53和C-Myc表达对弥漫大B细胞淋巴瘤相关噬血细胞综合征的预后影响[J]. 中国现代医生, 2023, 61(25): 5-8, 13.
[20] Cheng, W., Duan, L., Xu, J., et al.(2023) Prognostic Value of the Albumin-Bilirubin Score in Patients with Non-Hodgkin Lymphoma-Associated Hemophagocytic Lymphohistiocytosis. Frontiers in Immunology, 14, Article 1162320. [Google Scholar] [CrossRef] [PubMed]
[21] Janka, G.E. and Lehmberg, K. (2014) Hemophagocytic Syndromes—An Update. Blood Advances, 28, 135-142. [Google Scholar] [CrossRef] [PubMed]
[22] Bergsten, E., Horne, A., Aricó, M., et al. (2017) Confirmed Efficacy of Etoposide and Dexamethasone in HLH Treatment: Long-Term Results of the Cooperative HLH-2004 Study. Blood, 130, 2728-2738. [Google Scholar] [CrossRef] [PubMed]
[23] Johnson, T.S., Terrell, C.E., Millen, S.H., et al.(2014) Etoposide Selectively Ablates Activated Tcells to Control the Immunoregulatory Disorder Hemophagocytic Lymphohistiocytosis. Journal of Immunology, 192, 84-91. [Google Scholar] [CrossRef] [PubMed]
[24] Ellin, F., Landström, J., Jerkeman, M., et al. (2014) Real-World Data on Prognostic Factors and Treatment in Peripheral T-Cell Lymphomas: A Study from the Swedish Lymphoma Registry. Blood, 124, 1570-1577. [Google Scholar] [CrossRef] [PubMed]
[25] Song, Y., Wang, J., Wang, Y., et al. (2021) Requirement for Containing Etoposide in the Initial Treatment of Lymphoma Associated Hemophagocytic Lymphohistiocytosis. Cancer Biology & Therapy, 22, 598-606. [Google Scholar] [CrossRef] [PubMed]
[26] Meng, G., Wang, Y., Wang, J. and Wang, Z. (2021) the DEP Regimen Is Superior to the HLH-1994 Regimen as First-Line Therapy for Lymphoma-Associated Haemophagocytic Lymphohistiocytosis. Journal of Leukemia and Lymphoma, 62, 854-860. [Google Scholar] [CrossRef] [PubMed]
[27] Pi, Y., Wang, J., Zhou, H., et al. (2023) Modified DEP Regimen as Induction Therapy for Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Prospective, Multicenter Study. Journal of Cancer Research and Clinical Oncology, 149, 3033-3041. [Google Scholar] [CrossRef] [PubMed]
[28] Das, R., Guan, P., Sprague, L., et al. (2016) Janus Kinase Inhibition Lessens Inflammation and Ameliorates Disease in Murine Models of Hemophagocytic Lymphohistiocytosis. Blood, 127, 1666-1675. [Google Scholar] [CrossRef] [PubMed]
[29] Zhou, L., Liu, Y., Wen, Z., et al. (2020) Ruxolitinib Combined with Doxorubicin, Etoposide, and Dexamethasone for the Treatment of the Lymphoma-Associated Hemophagocytic Syndrome. Journal of Cancer Research and Clinical Oncology, 146, 3063-3074. [Google Scholar] [CrossRef] [PubMed]
[30] Zhou, D., Huang, X., Xie, M., et al. (2023) Ruxolitinib Combined with Dexamethasone in Adult Patients with Newly Diagnosed Hemophagocytic Lymphohistiocytosis: A Single-Center Pilot Trial. American Journal of Hematology, 98, E106-E109. [Google Scholar] [CrossRef] [PubMed]
[31] Meyer, L.K., Verbist, K.C., Albeituni, S., et al. (2020) JAK/STAT Pathway Inhibition Sensitizes CD8 T Cells to Dexamethasone-Induced Apoptosis in Hyperinflammation. Blood, 136, 657-668. [Google Scholar] [CrossRef] [PubMed]
[32] Stalder, G., Suffiotti, M., Segot, A., et al. (2023) Response-Adjusted Regimen Combining Ruxolitinib, Etoposide and Dexamethasone (AdRED) in Adult Patients with Acute Myeloid Leukemia-Associated Hemophagocytic Lymphohistiocytosis: A Single-Center Pilot Trial. Haematologica, 108, 234-239. [Google Scholar] [CrossRef] [PubMed]
[33] Wang, H., Fu, B.B., Gale, R.P., et al. (2021) NK-/T-Cell Lymphomas. Leukemia, 35, 2460-2468. [Google Scholar] [CrossRef] [PubMed]
[34] He, Y., Gao, Y., Ping, L., et al. (2023) The Emerging Role of Anti-PD-1 Antibody-Based Regimens in the Treatment of Extranodal NK/T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis. Journal of Cancer Research and Clinical Oncology, 149, 2017-2027. [Google Scholar] [CrossRef] [PubMed]
[35] Xu, Q.Y., Yang, H.Y., Li, M.W., et al. (2022) Sintilimab Combined with Chidamide in the Treatment of Extranodal Nature Killer/T-Cell Lymphoma with Secondary Hemophagocytic Lymphohistiocytosis: Two Case Reports and Literature Review. Medicine, 101, e30731. [Google Scholar] [CrossRef
[36] Faguer, S., Vergez, F., Peres, M., et al. (2016) Tocilizumab Added to Conventional Therapy Reverses Both the Cytokine Profile and CD8 Granzyme T-Cells/NK Cells Expansion in Refractory Hemophagocytic Lymphohistiocytosis. Journal of Hematology & Oncology, 34, 55-57. [Google Scholar] [CrossRef] [PubMed]
[37] Dufranc, E., Del Bello, A., Belliere, J., et al. (2020) IL6-R Blocking with Tocilizumab in Critically Ill Patients with Hemophagocytic Syndrome. Journal of Critical Care, 24, Article No. 166. [Google Scholar] [CrossRef] [PubMed]
[38] Kim, J.Y., Kim, M., Park, J.K., et al. (2022) Limited Efficacy of Tocilizumab in Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis: A Retrospective Cohort Study. Orphanet Journal of Rare Diseases, 17, Article No. 363. [Google Scholar] [CrossRef] [PubMed]