血液肿瘤患者结核分枝杆菌潜伏感染研究进展

doi:10.19982/j.issn.1000-6621.20250466

摘要/Abstract

摘要：

结核病是全球面临的重大公共卫生挑战之一,全球近四分之一的人口为结核分枝杆菌潜伏感染 (latent tuberculosis infection, LTBI)者,控制LTBI的主要对象为高危人群,目前其他免疫低下的高危人群研究较为完善,而血液肿瘤(hematological malignancy, HM)患者LTBI尚未引起足够的重视。HM患者由于自身疾病、大剂量化疗及移植预处理等原因,LTBI率明显高于普通人群,同时,LTBI可以增加HM的发生和死亡风险,临床上须予以重视。本文旨在对HM患者LTBI现状进行梳理,为临床医生进行诊断和预防性治疗提供依据,同时也指出其仍存在的研究空白。

关键词: 分枝杆菌, 结核, 感染, 血液肿瘤, 共病现象, 综述

Abstract:

Tuberculosis remains a global public health threat, with latent tuberculosis infection (LTBI) affecting nearly one in four individuals worldwide. While current control efforts appropriately target high-risk populations, LTBI has been extensively characterized in most immunocompromised groups-yet it remains markedly under-investigated in patients with haematological malignancies (HM). The profound immunosuppression intrinsic to the underlying disease, intensified by high-dose cytotoxic chemotherapy and hematopoietic stem-cell transplant conditioning, drives LTBI prevalence in this cohort well above that of the general population. Moreover, LTBI itself is increasingly recognized as an independent contributor to both the incidence and mortality of HM, underscoring the imperative for heightened clinical vigilance. This review synthesizes the contemporary evidence on LTBI in HM patients, providing an evidence-based framework to guide screening, diagnosis, and preventive therapy, and delineates the critical knowledge gaps that continue to impede optimal patient care.

Key words: Mycobacterium tuberculosis, Infection, Hematologic neoplasms, Comorbidity, Review

中图分类号:

胡鑫洋, 柳阳, 高静韬. 血液肿瘤患者结核分枝杆菌潜伏感染研究进展[J]. 中国防痨杂志, 2026, 48(5): 694-699. doi: 10.19982/j.issn.1000-6621.20250466

Hu Xinyang, Liu Yang, Gao Jingtao. Research progress on latent tuberculosis infection in patients with hematological malignancies[J]. Chinese Journal of Antituberculosis, 2026, 48(5): 694-699. doi: 10.19982/j.issn.1000-6621.20250466

参考文献 52

[1]	Al-Anazi KA, Al-Jasser AM, Evans DA. Infections caused by mycobacterium tuberculosis in patients with hematological disorders and in recipients of hematopoietic stem cell transplant, a twelve year retrospective study. Ann Clin Microbiol Antimicrob, 2007, 6:16. doi:10.1186/1476-0711-6-16.
[2]	Osorio-López EA, Vilar-Compte D, García-Tirado J, et al. Prevalence of latent tuberculosis in patients with hematological neoplasms in a cancer referral hospital in Mexico City. BMC Infect Dis, 2021, 21(1):510. doi:10.1186/s12879-021-06236-y. URL pmid: 34059022
[3]	Reifler KA, Francoeur Smith T, Bodanapu G, et al. Indolent infections in patients with hematologic malignancy: A single-center experience screening for tuberculosis and strongyloidiasis prior to cytotoxic therapy in Boston. Leuk Res Rep, 2024, 22:100489. doi:10.1016/j.lrr.2024.100489.
[4]	Kilicaslan E, Canoglu K. Management of Latent Tuberculosis Infection Based on T-SPOT.TB Assay in Patients with Hematological Malignancies. Mediterr J Hematol Infect Dis, 2023, 15(1):e2023003. doi:10.4084/MJHID.2023.003.
[5]	中国防痨协会. 高危人群结核分枝杆菌潜伏感染检测及预防性治疗专家共识. 中国防痨杂志, 2021, 43(9):874-878. doi:10.3969/j.issn.1000-6621.2021.09.004
[6]	马艳, 成诗明. 加速我国结核潜伏感染筛查与预防性治疗的建议. 实用医学杂志, 2023, 39(11):1335-1340. doi:10.3969/j.issn.1006-5725.2023.11.003.
[7]	中国医学科学院病原生物学研究所, 中国疾病预防控制中心, 中国科学院地理科学与资源研究所. 全国结核分枝杆菌潜伏感染率估算专家共识. 中国防痨杂志, 2022, 44(1):4-8. doi:10.19982/j.issn.1000-6621.20210662.
[8]	Aldabbagh MA, Abughasham A, Alansari G, et al. The Prevalence of Mycobacterium tuberculosis Infection Among Cancer Patients Receiving Chemotherapy in a Tertiary Care Center. Cureus, 2022, 14(11):e32068. doi:10.7759/cureus.32068.
[9]	Taha R, Kothari S, Foroutan F, et al. Implementation of a Routine Screening Program for Latent Tuberculosis Infection among Patients with Acute Leukemia at a Canadian Cancer Center. Curr Oncol, 2022, 29(12):9325-9334. doi:10.3390/curroncol29120731. URL pmid: 36547145
[10]	Bettelli F, Giusti D, Morselli M, et al. Epidemiology and clinical outcomes of latent tuberculosis infection in adults affected with acute leukemia or aplastic anemia: a retrospective single-center study. Ann Hematol, 2020, 99(9):2201-2203. doi:10.1007/s00277-020-04191-3. URL pmid: 32699943
[11]	Li G, Chen GL, Zhou Y, et al. Increased Risk of Lymphoma in Men or the Elderly Infected with Tuberculosis. Mediterr J Hematol Infect Dis, 2021, 13(1):e2021053. doi:10.4084/MJHID.2021.053.
[12]	Su VY, Yen YF, Pan SW, et al. Latent Tuberculosis Infection and the Risk of Subsequent Cancer. Medicine (Baltimore), 2016, 95(4):e2352. doi:10.1097/MD.0000000000002352.
[13]	Anibarro L, Pena A. Tuberculosis in patients with haematological malignancies. Mediterr J Hematol Infect Dis, 2014, 6(1):e2014026. doi:10.4084/MJHID.2014.026.
[14]	Wu CY, Hu HY, Pu CY, et al. Aerodigestive tract, lung and haematological cancers are risk factors for tuberculosis: an 8-year population-based study. Int J Tuberc Lung Dis, 2011, 15(1):125-130. pmid: 21276308
[15]	Colado A, Genoula M, Cougoule C, et al. Effect of the BTK inhibitor ibrutinib on macrophage- and γδ T cell-mediated response against Mycobacterium tuberculosis. Blood Cancer J, 2018, 8(11):100. doi:10.1038/s41408-018-0136-x. URL pmid: 30397191
[16]	Lin C, Xu G, Gao S, et al. Tuberculosis infection following immune checkpoint inhibitor treatment for advanced cancer: a case report and literature review. Front Immunol, 2023, 14:1162190. doi:10.3389/fimmu.2023.1162190.
[17]	Ahnach M, El Kodmiri Z, Mourabiti I, et al. Successful Management of Active Tuberculosis During Allogeneic Hematopoietic Stem Cell Transplantation in a Patient With Relapsed Acute Myeloid Leukemia: A Case Report and Literature Review. Cureus, 2025, 17(4):e82026. doi:10.7759/cureus.82026.
[18]	Al-Anazi KA, Al-Jasser AM, Alsaleh K. Infections Caused by Mycobacterium tuberculosis in Recipients of Hematopoietic Stem Cell Transplantation. Front Oncol, 2014, 4:231. doi:10.3389/fonc.2014.00231. URL pmid: 25207262
[19]	Shu CC, Hsu CL, Lee CY, et al. Comparison of the Prevalence of Latent Tuberculosis Infection among Non-Dialysis Patients with Severe Chronic Kidney Disease, Patients Receiving Dialysis, and the Dialysis-Unit Staff: A Cross-Sectional Study. PLoS One, 2015, 10(4):e0124104. doi:10.1371/journal.pone.0124104.
[20]	Nunzi A, Della Valle L, Lindfors Rossi EL, et al. Acute Leukemia and Latent Tuberculosis Infection in Italy: Quantiferon-Tb Test Screening in a Low Tuberculosis Incidence Country. Mediterr J Hematol Infect Dis, 2024, 16(1):e2024054. doi:10.4084/MJHID.2024.054.
[21]	Cheon J, Kim C, Park EJ, et al. Active tuberculosis risk associated with malignancies: an 18-year retrospective cohort study in Korea. J Thorac Dis, 2020, 12(9):4950-4959. doi:10.21037/jtd.2020.02.50. URL pmid: 33145069
[22]	温淑芳, 魏荣荣, 李浩然, 等. CD4⁺和CD8⁺T细胞在结核病免疫应答中的作用. 中国防痨杂志, 2024, 46(4):479-484. doi:10.19982/j.issn.1000-6621.20230452.
[23]	Esmail H, Riou C, Bruyn ED, et al. The Immune Response to Mycobacterium tuberculosis in HIV-1-Coinfected Persons. Annu Rev Immunol, 2018, 36:603-638. doi:10.1146/annurev-immunol-042617-053420. URL pmid: 29490165
[24]	谢周华, 韦柳迎, 董文逸, 等. HIV/AIDS合并结核分枝杆菌潜伏感染特征及影响因素分析. 中国热带医学, 2022, 22(8):739-743. doi:10.13604/j.cnki.46-1064/r.2022.08.10.
[25]	黄方, 郝思国. 急性髓系白血病患者外周血T淋巴细胞亚群的水平变化及临床意义. 第二军医大学学报, 2020, 41(5):546-550. doi:10.16781/j.0258-879x.2020.05.0546.
[26]	温丽, 王丽, 翟小颖, 等. 儿童急性淋巴细胞白血病化疗前后细胞免疫的变化及与人巨细胞病毒感染的关系. 标记免疫分析与临床, 2017, 24(2):171-174,225. doi:10.11748/bjmy.issn.1006-1703.2017.02.012.
[27]	李慧, 赵红英, 卢峰. 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. 湖南师范大学学报(医学版), 2020, 17(1):139-141. doi:10.3969/j.issn.1673-016X.2020.01.042.
[28]	Fujita K, Terashima T, Mio T. Anti-PD 1 Antibody Treatment and the Development of Acute Pulmonary Tuberculosis. J Thorac Oncol, 2016, 11(12):2238-2240. doi:10.1016/j.jtho.2016.07.006. URL pmid: 27423391
[29]	Suliman AM, Bek SA, Elkhatim MS, et al. Tuberculosis following programmed cell death receptor-1 (PD-1) inhibitor in a patient with non-small cell lung cancer. Case report and literature review. Cancer Immunol Immunother, 2021, 70(4):935-944. doi:10.1007/s00262-020-02726-1. URL pmid: 33070259
[30]	李军, 牛挺. 恶性血液病合并活动性结核病的临床研究进展. 中华血液学杂志, 2013, 34(12):1076-1079. doi:10.3760/cma.j.issn.0253-2727.2013.12.020.
[31]	Cheng MP, Abou Chakra CN, Yansouni CP, et al. Risk of Active Tuberculosis in Patients with Cancer: A Systematic Review and Meta-Analysis. Clin Infect Dis, 2017, 64(5):635-644. doi:10.1093/cid/ciw838. URL pmid: 27986665
[32]	Dobler CC, Cheung K, Nguyen J, et al. Risk of tuberculosis in patients with solid cancers and haematological malignancies: a systematic review and meta-analysis. Eur Respir J, 2017, 50(2): 1700157. doi:10.1183/13993003.00157-2017.
[33]	Aguado JM, Silva JT, Samanta P, et al. Tuberculosis and Transplantation. Microbiol Spectr, 2016, 4(6). doi:10.1128/microbiolspec.TNMI7-0005-2016.
[34]	Chen CY, Sheng WH, Cheng A, et al. Clinical characteristics and outcomes of Mycobacterium tuberculosis disease in adult patients with hematological malignancies. BMC Infect Dis, 2011, 11:324. doi:10.1186/1471-2334-11-324.
[35]	Ahn JS, Rew SY, Yang DH, et al. Poor prognostic significance of Mycobacterium tuberculosis infection during bortezomib-containing chemotherapy in patients with multiple myeloma. Blood Res, 2013, 48(1):35-39. doi:10.5045/br.2013.48.1.35.
[36]	Tsai CK, Huon LK, Ou SM, et al. Risk and impact of tuberculosis in patients with multiple myeloma. Leuk Lymphoma, 2017, 58(11):2598-2606. doi:10.1080/10428194.2017.1312369.
[37]	Liu CJ, Hong YC, Teng CJ, et al. Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan. Int J Cancer, 2015, 136(8):1881-1887. doi:10.1002/ijc.29201.
[38]	Iqbal P, Soliman A, De Sanctis V, et al. Association of tuberculosis in patients with chronic myeloid leukemia: a treatment proposal based on literature review. Expert Rev Hematol, 2021, 14(2):211-217. doi:10.1080/17474086.2021.1875818. URL pmid: 33433245
[39]	Lee YG, Seo D, Gil HI, et al. Risk of malignant lymphoma in patients with previous tuberculosis infection: a cohort study. Ann Hematol, 2025, 104(1):401-406. doi:10.1007/s00277-024-06159-z.
[40]	Ji X, Hu L, Wang Y, et al. Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials. Chin Med J (Engl), 2022, 135(4):409-415. doi:10.1097/CM9.0000000000001948.
[41]	Bergeron A, Mikulska M, De Greef J, et al. Mycobacterial infections in adults with haematological malignancies and haematopoietic stem cell transplants: guidelines from the 8th European Conference on Infections in Leukaemia. Lancet Infect Dis, 2022, 22(12):e359-e369. doi:10.1016/S1473-3099(22)00227-4. URL pmid: 35636446
[42]	Piana F, Codecasa LR, Cavallerio P, et al. Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients. Eur Respir J, 2006, 28(1):31-34. doi:10.1183/09031936.06.00110205. URL pmid: 16540502
[43]	Richeldi L, Losi M, D’Amico R, et al. Performance of tests for latent tuberculosis in different groups of immunocompromised patients. Chest, 2009, 136(1):198-204. doi:10.1378/chest.08-2575. URL pmid: 19318676
[44]	中华医学会结核病学分会. 结核分枝杆菌γ-干扰素释放试验及临床应用专家意见(2021年版). 中华结核和呼吸杂志, 2022, 45(2):143-150. doi:10.3760/cma.j.cn112147-20211110-00794.
[45]	Youssef J, Novosad SA, Winthrop KL. Infection Risk and Safety of Corticosteroid Use. Rheum Dis Clin North Am, 2016, 42(1):157-176, ix-x. doi:10.1016/j.rdc.2015.08.004.
[46]	李果, 庞先琼, 徐华, 等. 潜伏性结核感染诊治进展. 中国防痨杂志, 2021, 43(1):91-95. doi:10.3969/j.issn.1000-6621.2021.01.017
[47]	中华医学会结核病学分会, 《中华结核和呼吸杂志》编辑委员会. γ-干扰素释放试验在中国应用的建议. 中华结核和呼吸杂志, 2014, 37(10):744-747. doi:10.3760/cma.j.issn.1001-0939.2014.10.011.
[48]	González-Martín J, García-García JM, Anibarro L, et al. Consensus document on the diagnosis, treatment and prevention of tuberculosis. Enferm Infecc Microbiol Clin, 2010, 28(5):297.e1-20. doi:10.1016/j.arbres.2010.02.010.
[49]	World Health Organization. WHO consolidated guidelines on tuberculosis: Module 1: Prevention-Tuberculosis preventive treatment, second edition. Geneva: World Health Organization, 2024.
[50]	Krishnan S, Chaisson RE. US Guidelines Fall Short on Short-Course Tuberculosis-Preventive Therapy. Clin Infect Dis, 2024, 78(3):514-517. doi:10.1093/cid/ciad659.
[51]	Hohmann C, Kang EM, Jancel T. Rifampin and posaconazole coadministration leads to decreased serum posaconazole concentrations. Clin Infect Dis, 2010, 50(6):939-940. doi:10.1086/650740. URL pmid: 20166829
[52]	Sánchez-García EM, Gamallo R, Blanco-Moure A, et al. Toxicity and adherence to treatment for latent tuberculosis infection in patients with hematologic malignancies. Infection, 2013, 41(5):903-907. doi:10.1007/s15010-013-0489-9. URL pmid: 23737388