血液肿瘤患儿侵袭性真菌感染诊治和管理策略

doi:10.12372/jcp.2023.23e0416

Abstract

Abstract:

Invasive fungal disease (IFD) is one of the most common types of infection in the treatment of hematologic malignancies and has a significant impact on the prognosis of pediatric patients with hematologic malignancies. In recent years, with the development of pathogen molecular detection techniques and the application of new antifungal drugs, the prognosis of IFD in pediatric patients with hematologic malignancies has been greatly improved. However, challenges such as diagnostic difficulties, complex disease conditions, and the selection of treatment drugs still exist. This article summarizes the current research progress and the latest diagnostic and therapeutic guidelines to elucidate the risk factors, clinical features, treatment strategies, and prognosis of IFD in pediatric patients with hematologic malignancies, aiming to better assist pediatricians in understanding the prevention, management, and treatment of IFD in pediatric patients with hematologic malignancies.

Key words: invasive fungal disease, hematologic malignancies, diagnostic and therapeutic guidelines, treatment, child

SHEN Nan, DU Bailu. Strategies for the diagnosis, treatment, and management of invasive fungal infections in children with hematologic neoplasms[J].Journal of Clinical Pediatrics, 2023, 41(8): 571-577.

Figures/Tables 3

References 36

[1]	Olivier-Gougenheim L, Rama N, Dupont D, et al. Invasive fungal infections in immunocompromised children: novel insight following a national study[J]. J Pediatr, 2021, 236: 204-210. doi: 10.1016/j.jpeds.2021.05.016
[2]	Wang SS, Kotecha RS, Bernard A, et al. Invasive fungal infections in children with acute lymphoblastic leukaemia: results from four Australian centres, 2003-2013[J]. Pediatr Blood Cancer, 2019, 66(10): e27915.
[3]	Czyżewski K, Gałązka P, Frączkiewicz J, et al. Epidemiology and outcome of invasive fungal disease in children after hematopoietic cell transplantation or treated for malignancy: impact of national programme of antifungal prophylaxis[J]. Mycoses, 2019, 62(11): 990-998. doi: 10.1111/myc.12990 pmid: 31429997
[4]	Groll AH, Pana D, Lanternier F, et al. 8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation[J]. Lancet Oncol, 2021, 22(6): e254-e269.
[5]	Teh BW, Yeoh DK, Haeusler GM, et al. Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021[J]. Intern Med J, 2021, 51 (Suppl 7): 67-88. doi: 10.1111/imj.v51.S7
[6]	Hol JA, Wolfs TF, Bierings MB, et al. Predictors of invasive fungal infection in pediatric allogeneic hematopoietic SCT recipients[J]. Bone Marrow Transplant, 2014, 49(1): 95-101. doi: 10.1038/bmt.2013.136
[7]	Kobayashi R, Kaneda M, Sato T, et al. Evaluation of risk factors for invasive fungal infection after allogeneic stem cell transplantation in pediatric patients[J]. J Pediatr Hematol Oncol, 2007, 29(11): 786-791. doi: 10.1097/MPH.0b013e318142b598
[8]	Sun Y, Meng F, Han M, et al. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in china: a multicenter prospective observational study[J]. Biol Blood Marrow Transplant, 2015, 21(6): 1117-1126. doi: 10.1016/j.bbmt.2015.03.018
[9]	Bartlett AW, Cann MP, Yeoh DK, et al. Epidemiology of invasive fungal infections in immunocompromised children; an Australian national 10-year review[J]. Pediatr Blood Cancer, 2019, 66(4): e27564.
[10]	Xiao M, Chen SC, Kong F, et al. Distribution and antifungal susceptibility of Candida species causing candidemia in China: an update from the CHIF-NET study[J]. J Infect Dis, 2020, 221(Suppl 2): S139-S147.
[11]	Otto WR, Green AM. Fungal infections in children with haematologic malignancies and stem cell transplant recipients[J]. Br J Haematol, 2020, 189(4): 607-624. doi: 10.1111/bjh.v189.4
[12]	中国医药教育学会真菌病专业委员会中华医学会血液学分会. 造血干细胞移植后侵袭性真菌病中国专家共识(2023年版)[J]. 中华血液学杂志, 2023, 44(2): 92-97.
[13]	Puerta-Alcalde P, Garcia-Vidal C. Changing epidemiology of invasive fungal disease in allogeneic hematopoietic stem cell transplantation[J]. J Fungi (Basel), 2021, 7(10): 848.
[14]	Hale KA, Shaw PJ, Dalla-Pozza L, et al. Epidemiology of paediatric invasive fungal infections and a case-control study of risk factors in acute leukaemia or post stem cell transplant[J]. Br J Haematol, 2010, 149(2): 263-272. doi: 10.1111/bjh.2010.149.issue-2
[15]	中国医师协会血液科医师分会中国侵袭性真菌感染工作组. 血液病/恶性肿瘤患者侵袭性真菌病的诊断标准与治疗原则(第六次修订版)[J]. 中华内科杂志, 2020, 59(10): 754-763.
[16]	Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium[J]. Clin Infect Dis, 2020, 71(6): 1367-1376. doi: 10.1093/cid/ciz1008 pmid: 31802125
[17]	De Pauw B, Walsh TJ, Donnelly JP, et al. revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group[J]. Clin Infect Dis, 2008, 46(12): 1813-1821. doi: 10.1086/588660 pmid: 18462102
[18]	中国医药教育协会真菌病专业委员会, 中国毛霉病专家共识工作组. 中国毛霉病临床诊疗专家共识(2022)[J]. 中华内科杂志, 2023, 62(6): 597-605.
[19]	Giacobbe DR, Del Bono V, Viscoli C, et al. Use of 1,3-β-D-glucan in invasive fungal diseases in hematology patients[J]. Expert Rev Anti Infect Ther, 2017, 15(12): 1101-1112. doi: 10.1080/14787210.2017.1401467 pmid: 29125373
[20]	Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline[J]. Clin Microbiol Infect, 2018, 24(Suppl 1): e1-e38.
[21]	Cruciani M, Mengoli C, Loeffler J, et al. Polymerase chain reaction blood tests for the diagnosis of invasive aspergillosis in immunocompromised people[J]. Cochrane database Syst Rev, 2015, (9): CD009551.
[22]	Peng JM, Du B, Qin HY, et al. Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients[J]. J Infect, 2021, 82(4): 22-27. doi: 10.1016/j.jinf.2021.01.029
[23]	Zinter MS, Dvorak CC, Mayday MY, et al. Pulmonary metagenomic sequencing suggests missed infections in immunocompromised children[J]. Clin Infect Dis, 2019, 68(11): 1847-1855. doi: 10.1093/cid/ciy802 pmid: 30239621
[24]	Gu W, Deng X, Lee M, et al. Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids[J]. Nat Med, 2021, 27(1): 115-124. doi: 10.1038/s41591-020-1105-z pmid: 33169017
[25]	中国医药教育协会真菌病专业委员会, 国家皮肤与免疫疾病临床医学研究中心(北京大学第一医院), 国家血液疾病临床医学研究中心(北京大学人民医院). 侵袭性真菌病实验室诊断方法临床应用专家共识[J]. 中华内科杂志, 2022, 61(2): 134-141.
[26]	中国成人念珠菌病诊断与治疗专家共识组. 中国成人念珠菌病诊断与治疗专家共识[J]. 中华传染病杂志 2020 ; 38(1): 29-43.
[27]	Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients[J]. Haematologica, 2017, 102(3): 433-444. doi: 10.3324/haematol.2016.152900 pmid: 28011902
[28]	Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2016, 62: e1-e50. doi: 10.1093/cid/civ933
[29]	Ledoux MP, Herbrecht R. Invasive pulmonary aspergillosis[J]. J Fungi (Basel), 2023, 9(2): 131.
[30]	Hoenigl M, Salmanton-García J, Walsh TJ, et al. Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiolo[J]. Lancet Infect Dis, 2021, 21(8): e246-e257. doi: 10.1016/S1473-3099(20)30784-2 pmid: 33606997
[31]	Kamboj M, Weinstock D, Sepkowitz KA. Progression of Pneumocystis jiroveci pneumonia in patients receiving echinocandin therapy[J]. Clin Infect Dis, 2006, 43(9): e92-e94.
[32]	Yi WM, Schoeppler KE, Jaeger J, et al. Voriconazole and posaconazole therapeutic drug monitoring: a retrospective study[J]. Ann Clin Microbiol Antimicrob, 2017, 16(1): 60. doi: 10.1186/s12941-017-0235-8
[33]	Pana ZD, Roilides E. Risk of azole-enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: old problem - new dilemma[J]. Pediatr Blood Cancer, 2011, 57(1): 30-35. doi: 10.1002/pbc.22972 pmid: 21265011
[34]	Marr KA, Leisenring W, Crippa F, et al. Cyclophosphamide metabolism is affected by azole antifungals[J]. Blood, 2004, 103(4): 1557-1559. doi: 10.1182/blood-2003-07-2512 pmid: 14504090
[35]	Saad AH, DePestel DD, Carver PL. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants[J]. Pharmacotherapy, 2006, 26(12): 1730-1744. pmid: 17125435
[36]	Ceberio I, Dai K, Devlin SM, et al. Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT[J]. Bone Marrow Transplant, 2015, 50(3): 438-443. doi: 10.1038/bmt.2014.286

风险水平	风险因素
高风险（>10%）	AML、复发性急性白血病、高风险急性淋巴细胞白血病（ALL）^1）、异体HSCT、GVHD
低风险（<5%）	标准风险或低风险ALL、非霍奇金淋巴瘤、自体HSCT
极低风险	霍奇金淋巴瘤、小儿实体肿瘤、脑肿瘤
未知	CAR-T细胞治疗、其他免疫疗法

病原体	一线治疗	替代方案
念珠菌病
念珠菌血症	棘白菌类、两性霉素B脂质体	伏立康唑、伊曲康唑、氟康唑
播散性念珠菌病	中性粒细胞缺乏：棘白菌类、两性霉素B脂质体、伏立康唑无中性粒细胞缺乏：氟康唑、伊曲康唑	— ?
中枢神经系统念珠菌病	两性霉素B脂质体、伏立康唑	氟康唑
曲霉菌病
初始治疗	伏立康唑	两性霉素 B 脂质体
挽救治疗	两性霉素 B 脂质体、泊沙康唑、伊曲康唑	卡泊芬净、米卡芬净
预防治疗	泊沙康唑、伏立康唑、伊曲康唑	卡泊芬净、米卡芬净
毛霉病
初始治疗	两性霉素B脂质体、两性霉素B脂质体联合泊沙康唑	泊沙康唑静脉制剂
挽救治疗	泊沙康唑静脉制剂	泊沙康唑肠溶片或口服混悬液
其他少见真菌
耶氏肺孢子菌	复方磺胺甲噁唑	克林霉素联合伯氨喹、卡泊芬净
马尔尼菲篮状菌	两性霉素B脂质体联合/不联合伊曲康唑	伏立康唑
镰刀菌病	伏立康唑、伏立康唑联合两性霉素B脂质体、伏立康唑联合两性霉素B脂质复合物	两性霉素B脂质体、两性霉素B脂质复合物
赛多孢子菌病	伏立康唑	伏立康唑联合两性霉素B脂质体或两性霉素B脂质复合物
播散性暗色丝孢霉病	泊沙康唑、伏立康唑联合棘白菌类、伏立康唑联合特比萘芬	两性霉素B脂质体联合/不联合棘白菌类或特比萘芬
帚霉感染	伏立康唑	两性霉素B脂质体联合/不联合伏立康唑
播散性青霉菌病	两性霉素B脂质体（联合/不联合其它抗真菌药物）	—

Strategies for the diagnosis, treatment, and management of invasive fungal infections in children with hematologic neoplasms

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