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瓜氨酸作为儿童急性淋巴细胞白血病诱导治疗期间菌血症的生物标志物。

Citrulline as a biomarker of bacteraemia during induction treatment for childhood acute lymphoblastic leukaemia.

机构信息

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

Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Pediatr Blood Cancer. 2021 Jan;68(1):e28793. doi: 10.1002/pbc.28793. Epub 2020 Nov 5.

Abstract

BACKGROUND

Systemic infections are a major cause of morbidity in children with acute lymphoblastic leukaemia (ALL). However, identification of patients at increased risk is still a challenge. Knowing that both neutropaenia and gastrointestinal toxicity are risk factors for bacteraemia, we aimed at comparing absolute neutrophil counts (ANC) and plasma citrulline levels (indicating enterocyte loss) in children with ALL with and without bacteraemia during induction treatment.

PROCEDURE

We prospectively included 61 children with ALL treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol. ANC and plasma C-reactive protein (CRP) were measured on treatment days 1, 8, 15, 22 and 29. Plasma citrulline was measured on days 1, 8, 15 and 29. Bacteraemia episodes during induction treatment were recorded retrospectively.

RESULTS

Nineteen of sixty-one (31%) patients experienced bacteraemia occurring on median day 13 (range 5-20). Patients with bacteraemia during induction treatment had lower citrulline level on day 15 (P < .01) compared to patients without bacteraemia, indicating more severe enterocyte loss. Nevertheless, ANC was similar in the two patient groups on days 8 and 15. CRP was negatively correlated with same-day citrulline (P < .03 for all) and ANC (P < .04 for all).

CONCLUSIONS

During chemotherapy-induced neutropaenia, plasma citrulline may help identify patients at increased risk of bacteraemia.

摘要

背景

全身性感染是儿童急性淋巴细胞白血病(ALL)发病和死亡的主要原因。然而,目前仍难以准确识别高危患者。已知中性粒细胞减少和胃肠道毒性均为菌血症的危险因素,因此我们旨在比较诱导治疗期间伴有和不伴有菌血症的 ALL 患儿的绝对中性粒细胞计数(ANC)和血浆瓜氨酸水平(提示肠上皮细胞丢失)。

方法

我们前瞻性纳入了 61 例按照北欧小儿血液和肿瘤学会(NOPHO)ALL-2008 方案治疗的 ALL 患儿。在治疗第 1、8、15、22 和 29 天检测 ANC 和血浆 C 反应蛋白(CRP),在第 1、8、15 和 29 天检测血浆瓜氨酸。回顾性记录诱导治疗期间的菌血症发作情况。

结果

61 例患儿中有 19 例(31%)发生菌血症,中位发生时间为第 13 天(范围为 5-20 天)。诱导治疗期间发生菌血症的患儿在第 15 天的瓜氨酸水平较低(P<.01),提示肠上皮细胞丢失更严重。然而,两组患儿在第 8 天和第 15 天的 ANC 相似。CRP 与同日瓜氨酸(所有 P<.03)和 ANC(所有 P<.04)呈负相关。

结论

在化疗诱导的中性粒细胞减少期间,血浆瓜氨酸可能有助于识别菌血症风险增加的患者。

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