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胃肠道屏障完整性和黏膜炎症作为急性淋巴细胞白血病患儿治疗后血流感染的危险因素。

Gastrointestinal barrier integrity and mucosal inflammation as risk factors of blood stream infections in children treated for acute lymphoblastic leukaemia.

机构信息

Department of Paediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Institute for Inflammation Research, Center for Rheumatology and Spine Disease, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Int J Cancer. 2023 Nov 1;153(9):1635-1642. doi: 10.1002/ijc.34639. Epub 2023 Jun 30.

Abstract

Chemotherapy-induced mucositis increases the risk of blood stream infections (BSI) due to translocation of bacteria across the intestinal epithelium. Our study investigated if quantitative measures of intestinal mucositis severity, including plasma citrulline (a marker of functional enterocytes) and CCL20 (an intestinal immune homeostatic chemokine), could identify patients at risk of BSI. A total of 106 children with ALL undergoing induction treatment (NOPHO ALL 2008) were included and information regarding BSI episodes was collected from the patients' medical records. Twenty-seven patients (25%) developed BSI during induction. Patients with BSI had a larger decrease in citrulline after chemotherapy than patients without BSI, and nearly all BSI episodes (25/27) occurred in the group of patients exhibiting a drop in citrulline (OR = 6.4 [95% CI: 1.4-29.3], P = .008). Patients who developed BSI had higher plasma CCL20 levels on days 8, 15 and 22 than patients without BSI (all P < .05), and elevated CCL20 levels on day 8 increased the risk of subsequent BSI (OR = 1.57 [1.11-2.22] per doubling of CCL20 level, P = .01) in a multivariable logistic regression analysis. These findings suggest that children with ALL who develop BSI during chemotherapy are characterised by more severe intestinal mucositis, as measured by plasma citrulline and CCL20. These markers may be useful in early risk stratification to guide treatment decisions.

摘要

化疗诱导的粘膜炎会增加血流感染 (BSI) 的风险,这是由于细菌穿过肠上皮细胞易位所致。我们的研究调查了肠道粘膜炎严重程度的定量测量,包括血浆瓜氨酸(功能肠细胞的标志物)和 CCL20(肠道免疫稳态趋化因子),是否可以识别有 BSI 风险的患者。共有 106 名接受诱导治疗的 ALL 患儿(NOPHO ALL 2008)被纳入研究,并从患者的病历中收集了有关 BSI 发作的信息。27 名患者(25%)在诱导期发生 BSI。与无 BSI 的患者相比,发生 BSI 的患者在化疗后瓜氨酸下降幅度更大,几乎所有 BSI 发作(25/27)均发生在瓜氨酸下降的患者组(OR=6.4 [95%CI: 1.4-29.3],P=0.008)。与无 BSI 的患者相比,发生 BSI 的患者在第 8、15 和 22 天的血浆 CCL20 水平更高(均 P<0.05),并且第 8 天的 CCL20 水平升高会增加随后发生 BSI 的风险(OR=1.57 [1.11-2.22],每增加 CCL20 水平一倍,P=0.01),这在多变量逻辑回归分析中得到证实。这些发现表明,在化疗期间发生 BSI 的 ALL 患儿,其肠道粘膜炎更为严重,血浆瓜氨酸和 CCL20 均可测量。这些标志物可能有助于早期风险分层,指导治疗决策。

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