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β-D-葡聚糖在儿科癌症患者慢性播散性念珠菌病诊断及反应监测中的应用与陷阱

Utility and Pitfalls of β-D-Glucan for Diagnosis and Response Monitoring of Chronic Disseminated Candidiasis in Paediatric Cancer Patients.

作者信息

Körholz Katharina F, Hennies Marc T, Herbrüggen Heidrun, Krämer Katja, Ahlmann Martina, Fröhlich Birgit, Schaumburg Frieder, Wiesel Thomas, Rath Peter M, Groll Andreas H

机构信息

Infectious Disease Research Program, Center for Bone Marrow Transplantation and Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany.

Institute of Virology, University Hospital Münster, Münster, Germany.

出版信息

Mycoses. 2025 Aug;68(8):e70102. doi: 10.1111/myc.70102.

Abstract

BACKGROUND

β-D-Glucan (BDG) is a useful but nonspecific biomarker in patients with suspected invasive fungal diseases including Pneumocystis pneumonia. Little is known, however, about its utility for response monitoring in chronic disseminated candidiasis (CDC).

PATIENTS AND METHODS

We describe the utility and pitfalls of serum BDG in paediatric cancer patients with suspected CDC. BDG in serum was measured serially (i.e., 5 to 10 times of a time period of 200 to 400 days) by a commercially available assay (Fungitell; Associates of Cape Cod, MA, USA) and values were correlated to patient- and disease-related variables.

RESULTS

Five paediatric patients (4f/1 m; 4-18 years) with acute lymphoblastic leukaemia (n = 4) and Ewing sarcoma (n = 1) followed between 2013 and 2024 were included. CDC was located in the spleen (n = 5), liver (n = 4), lungs (n = 3), CNS (n = 2), kidney (n = 1), and skin (n = 1); and diagnosed based on imaging, a positive blood culture (n = 1), a positive BDG assay in serum (n = 5), and absence of other etiologies. Patients received IV liposomal amphotericin B and/or caspofungin, followed by fluconazole orally for 184 to > 365 days, respectively. BDG concentrations in serum (35 time points) stayed elevated for prolonged periods of time, were independent of clinical symptoms, and returned to normal with resolution of imaging findings in the four leukaemia patients. In the patient with Ewing sarcoma, liver biopsy performed 5 months after diagnosis due to lack of improvement revealed disseminated aspergillosis.

CONCLUSIONS

BDG in serum is useful for microbiological diagnosis and monitoring of probable CDC; however, it remains a non-specific fungal biomarker whose results need to be scrutinised in patients who do not respond to treatment as expected.

摘要

背景

β - D - 葡聚糖(BDG)是疑似侵袭性真菌病患者(包括肺孢子菌肺炎)中一种有用但非特异性的生物标志物。然而,关于其在慢性播散性念珠菌病(CDC)反应监测中的效用知之甚少。

患者与方法

我们描述了血清BDG在疑似CDC的儿科癌症患者中的效用及陷阱。通过市售检测方法(Fungitell;美国马萨诸塞州科德角联合公司)对血清中的BDG进行连续检测(即在200至400天的时间段内检测5至10次),并将检测值与患者及疾病相关变量进行关联。

结果

纳入了2013年至2024年期间随访的5名儿科患者(4名女性/1名男性;4至18岁),其中急性淋巴细胞白血病患者4名,尤因肉瘤患者1名。CDC累及脾脏(5例)、肝脏(4例)、肺部(3例)、中枢神经系统(2例)、肾脏(1例)和皮肤(1例);根据影像学检查、血培养阳性(1例)、血清BDG检测阳性(5例)以及排除其他病因进行诊断。患者分别接受静脉注射脂质体两性霉素B和/或卡泊芬净治疗,随后口服氟康唑,疗程分别为184天至超过365天。血清BDG浓度(35个时间点)在较长时间内持续升高,与临床症状无关,4例白血病患者的影像学表现恢复正常时,BDG浓度也恢复正常。在尤因肉瘤患者中,由于病情无改善,诊断后5个月进行肝脏活检,结果显示为播散性曲霉病。

结论

血清BDG对可能的CDC的微生物学诊断和监测有用;然而,它仍然是一种非特异性真菌生物标志物,对于未按预期对治疗产生反应的患者,其结果需要仔细审查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ce7/12334987/6bb58c363a64/MYC-68-e70102-g001.jpg

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