Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia: a multicentre retrospective Australian cohort study

IF 7.6 1区 医学 Q1 HEALTH CARE SCIENCES & SERVICES The Lancet Regional Health: Western Pacific Pub Date : 2024-09-12 DOI:10.1016/j.lanwpc.2024.101201
Daniel K. Yeoh , Christopher C. Blyth , Julia E. Clark , Joanne Abbotsford , Claudia Corrente , Sara Cook , Rishi S. Kotecha , Stacie S. Wang , Tim Spelman , Monica A. Slavin , Karin A. Thursky , Gabrielle M. Haeusler
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Abstract

Background

Invasive fungal disease (IFD) is a significant complication for children receiving treatment for leukaemia, contributing to morbidity and mortality. Recent regional paediatric epidemiological IFD data are lacking. Additionally uncertainty remains regarding the optimal prophylactic approach in this context.

Methods

In a multi-centre Australian cohort study of children diagnosed with de novo acute leukaemia between 1st January 2017 and 30th June 2020, we characterised antifungal prophylaxis prescribing and IFD prevalence. Impact of antifungal prophylaxis was assessed using Kaplan Meier curves and Cox-proportional hazards regression adjusting for known IFD risk factors.

Findings

A total of 434 children were included (47.2% female; median age 5.0 years, median follow-up 240 days). This cohort included 351 children with ALL (214 high-risk [HR-ALL]; 137 standard-risk [SR-ALL]), and 73 with AML. The prevalence of proven/probable IFD was 6.8% for AML, 14.0% for HR-ALL and 4.4% for SR-ALL. A mould was implicated as the causative pathogen in almost two thirds of cases. Antifungal prophylaxis was prescribed in 98.7% of chemotherapy cycles for AML, 56.7% for HR-ALL and 14.9% for SR-ALL. A mould-active agent was used in 77.4% of AML cycles and 21.2% of HR-ALL cycles. Mould-active prophylaxis was associated with a lower risk of IFD overall and increased IFD-free survival in AML.

Interpretation

These data demonstrate the persistent high regional burden of IFD in children with HR-ALL, and the potential for mould-active prophylaxis to ameliorate this. Strategies to increase uptake of appropriate prophylaxis are required in this cohort.

Funding

This study was supported by a Perth Children’s Hospital Foundation grant (PCHF9973).

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急性白血病患儿的侵袭性真菌病和抗真菌预防:澳大利亚多中心回顾性队列研究
背景侵袭性真菌病(IFD)是接受白血病治疗的儿童的一个重要并发症,可导致发病率和死亡率。目前缺乏最新的地区性儿科 IFD 流行病学数据。方法 在一项澳大利亚多中心队列研究中,我们对 2017 年 1 月 1 日至 2020 年 6 月 30 日期间诊断为新发急性白血病的儿童进行了调查,了解了抗真菌预防处方的特点和 IFD 的流行情况。采用卡普兰-梅耶尔曲线和Cox比例危害回归评估了抗真菌预防的影响,并对已知的IFD风险因素进行了调整。研究结果共纳入434名儿童(47.2%为女性;中位年龄5.0岁,中位随访240天)。该队列包括351名ALL患儿(214名高风险[HR-ALL];137名标准风险[SR-ALL])和73名AML患儿。经证实/可能的IFD发病率分别为:AML 6.8%、HR-ALL 14.0%、SR-ALL 4.4%。近三分之二的病例的致病菌为霉菌。98.7%的AML化疗周期、56.7%的HR-ALL化疗周期和14.9%的SR-ALL化疗周期使用了抗真菌预防药物。77.4%的AML周期和21.2%的HR-ALL周期使用了霉菌活性药物。这些数据表明,在HR-ALL患儿中,IFD的区域性负担持续较高,而霉菌活性预防剂则有可能改善这一状况。这项研究得到了珀斯儿童医院基金会的资助(PCHF9973)。
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来源期刊
The Lancet Regional Health: Western Pacific
The Lancet Regional Health: Western Pacific Medicine-Pediatrics, Perinatology and Child Health
CiteScore
8.80
自引率
2.80%
发文量
305
审稿时长
11 weeks
期刊介绍: The Lancet Regional Health – Western Pacific, a gold open access journal, is an integral part of The Lancet's global initiative advocating for healthcare quality and access worldwide. It aims to advance clinical practice and health policy in the Western Pacific region, contributing to enhanced health outcomes. The journal publishes high-quality original research shedding light on clinical practice and health policy in the region. It also includes reviews, commentaries, and opinion pieces covering diverse regional health topics, such as infectious diseases, non-communicable diseases, child and adolescent health, maternal and reproductive health, aging health, mental health, the health workforce and systems, and health policy.
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