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小儿急性淋巴细胞白血病肠道损伤生物标志物的评估

Evaluation of biomarkers for intestinal damage in pediatric acute lymphoblastic leukemia.

作者信息

Kairiene Igne, Tarutyte Gabriele, Vaisnore Ramune, Kaminskas Andrius, Petrenas Tomas, Songailiene Jurgita, Eidukaite Audrone, Gorbikova Evelina, Rascon Jelena

机构信息

Faculty of Medicine, Vilnius University, Vilnius, Lithuania.

Center for Pediatric Oncology and Hematology, Vilnius University, Vilnius University Hospital Santaros Klinikos, Santariskiu 4, Vilnius, 08406, Lithuania.

出版信息

Sci Rep. 2025 May 15;15(1):16899. doi: 10.1038/s41598-025-98947-4.

DOI:10.1038/s41598-025-98947-4
PMID:40374880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12081597/
Abstract

Intestinal damage (ID) leads to bacterial translocation and bloodstream infections-the common cause of non-relapse mortality in childhood acute lymphoblastic leukemia (ALL). This study evaluated ID over ALL induction and the significance of body mass index (BMI) for its development and identified biomarkers reflecting chemotherapy-induced ID. The composite biomarker panel included 37 plasma amino acids, urea, ammonia, fecal calprotectin (fCLP), absolute neutrophil count (ANC), C-reactive protein, and albumin. We prospectively assessed 45 children treated according to the ALLTogether protocol in 2020-2024. Analysis and sample collection were performed on days 1, 8, 15, 22, and 29 of the protocol. The obtained values were compared between the ID and non-ID groups. 40% of patients (18/45) had grade I-III ID which was more pronounced on day 22 of induction when the ANC increased from its lowest point. Age younger than 5.5 years at a diagnosis was a significant prognostic factor for ID. Decreasing BMI and concentrations of citrulline, taurine, cystine, phosphoethanolamine, A-aminobutyric acid, B-alanine, and albumin suggest progressive ID in children treated due to ALL. No difference in ANC and fCLP was found between patients with and without ID, but fCLP levels start to rise simultaneously as the most intense ID is observed. In conclusion, assessing nutritional status and prospective evaluation of biomarkers may provide valuable information on treatment-related ID.

摘要

肠道损伤(ID)会导致细菌移位和血流感染,这是儿童急性淋巴细胞白血病(ALL)非复发死亡率的常见原因。本研究评估了ALL诱导治疗期间的ID情况及其发展过程中体重指数(BMI)的意义,并确定了反映化疗所致ID的生物标志物。复合生物标志物组包括37种血浆氨基酸、尿素、氨、粪便钙卫蛋白(fCLP)、绝对中性粒细胞计数(ANC)、C反应蛋白和白蛋白。我们前瞻性地评估了2020年至2024年期间按照ALLTogether方案治疗的45名儿童。在方案的第1、8、15、22和29天进行分析和样本采集。比较ID组和非ID组获得的值。40%的患者(18/45)有I-III级ID,在诱导治疗的第22天更为明显,此时ANC从最低点开始上升。诊断时年龄小于5.5岁是ID的一个重要预后因素。BMI降低以及瓜氨酸、牛磺酸、胱氨酸、磷酸乙醇胺、γ-氨基丁酸、β-丙氨酸和白蛋白浓度降低表明,因ALL接受治疗的儿童存在进行性ID。在有ID和无ID的患者之间,未发现ANC和fCLP有差异,但在观察到最严重的ID时,fCLP水平开始同时升高。总之,评估营养状况和对生物标志物进行前瞻性评估可能为与治疗相关的ID提供有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/5dcfc586d8d8/41598_2025_98947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/7cd9848ded15/41598_2025_98947_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/5dcfc586d8d8/41598_2025_98947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/7cd9848ded15/41598_2025_98947_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/4553bf30e127/41598_2025_98947_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/168b4a071e25/41598_2025_98947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9680/12081597/74f9735a6087/41598_2025_98947_Fig4_HTML.jpg
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