Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study

Olivier‐Gougenheim, Laura; Rama, Nicolas; Dupont, Damien; Saultier, Paul; Leverger, Guy; Abou-Chahla, Wadih; Paillard, Catherine; Gandemer, Virginie; Théron, Alexandre; Freyçon, Claire; Pluchart, Claire; Blouin, P.; Pellier, Isabelle; Thouvenin-Doulet, Sandrine; Desplantes, Claire; Ducassou, Stéphane; Oudot, Caroline; Rouger-Gaudichon, Jérémie; Cheikh, Nathalie; Poirée, Maryline; Schneider, Pascale; Plat, Geneviève; Contet, Audrey; Rialland, Fanny; Gouache, Elodie; Brethon, Benoît; Bertrand, Yves; Domenech, Carine

doi:10.1016/j.jpeds.2021.05.016

Cited by 14 publications

(14 citation statements)

References 49 publications

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“…These differences can be explained, at least in part, by the fact that the studies, all of which included considerably fewer patients than the present clinical trial, varied by the use of diagnostic tools and definition of IFD [ 15 , 18 – 20 ]. In addition, local epidemiology has an important impact on both the risk for IFD and the predominant pathogen isolated, as also supported by the data of our multi-international trial [ 8 , 15 , 17 , 18 , 20 , 21 ]. Our analysis demonstrated by both univariate and multivariate analysis that older age is associated with a higher risk for IFD.…”

Section: Discussionsupporting

confidence: 71%

“…In the prospective, randomized multi-international clinical trial AIEOP-BFM ALL2009 enrolling 6136 children with ALL, the reported overall incidence of proven/probable IFD and proven/probable/possible IFD was 3.8% and 6.2%, respectively, but was significantly higher in various subgroups, e.g., in older children and adolescents or in patients with insufficient early treatment response. The reported incidence rates of IFD in children with ALL vary widely across previous studies with rates reaching from 3.8% to up to 24% [ 15 – 17 ]. These differences can be explained, at least in part, by the fact that the studies, all of which included considerably fewer patients than the present clinical trial, varied by the use of diagnostic tools and definition of IFD [ 15 , 18 – 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, we do not have data on the use of antifungal prophylaxis, which may have impacted on the incidence for IFD. On the other hand, in contrast to AML [ 33 , 34 ], data on a significant effect of antifungal prophylaxis in patients with ALL is lacking for both children and adults [ 17 , 35 ], and widely used prophylactic options such as the intermittent administration of liposomal amphotericin B or micafungin have not demonstrated significant antifungal efficacy in any randomized trial [ 36 , 37 ]. Another limitation of our study is the fact that the use of important diagnostic tools such as pulmonary CT scan or galactomannan testing was at the discretion of the institution where the patient was treated, which is an inherent problem of all analyses of uncontrolled data.…”

Section: Discussionmentioning

confidence: 99%

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Invasive fungal diseases impact on outcome of childhood ALL – an analysis of the international trial AIEOP-BFM ALL 2009

et al. 2022

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In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Invasive fungal diseases impact on outcome of childhood ALL – an analysis of the international trial AIEOP-BFM ALL 2009

et al. 2022

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“…However, as stated in the guideline, the local epidemiology is an important consideration to design local approaches for the management of invasive fungal diseases (IFDs), and considering patients’ individual risk factors is also essential for best management. The incidence of IFIs, specific local ecology, different pharmacokinetics and drug interactions in the pediatric population should also lead to an assessment of the benefit–risk balance before initiating this treatment on a routine basis [ 13 , 25 ]. In our tertiary reference center, the strategy is based on environmental prophylaxis during all the HCT procedures, without systematic primary prophylaxis.…”

Section: Introductionmentioning

confidence: 99%

New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study

Ricard

Zebali

Rénard

et al. 2023

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Background: Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. Methods: We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. Results: 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. Conclusions: IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.

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“…Invasive fungal infection (IFI) is a significant cause of morbidity and mortality. In immunocompromised children, the incidence of IFI ranges from 5.3% to 24% [ 1 , 2 , 3 , 4 , 5 , 6 ] and the mortality rate is approximately 18.6% to 67.6% [ 2 , 3 , 7 , 8 ]. Early recognition and detection are crucial in managing IFI [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Combination of C-Reactive Protein and Procalcitonin in Distinguishing Fungal from Bacterial Infections Early in Immunocompromised Children

et al. 2022

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Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to access the diagnostic performance of C-reactive protein (CRP) and procalcitonin (PCT) in differentiating IFI from bacterial bloodstream infections in children with malignant and hematology disorders. CRP and PCT levels were measured in samples taken from patients between 12 and 24 h after fever onset, of which 24 and 102 were in the IFI and bacterial groups, respectively. We found that the CRP levels were much higher in the IFI group than the bacterial group (100.57 versus 40.04 mg/L, median, p < 0.001), while the PCT levels remained significantly lower (0.45 versus 1.29 μg/L, median, p = 0.007). Both CRP and PCT showed significant diagnostic utilities with an area under the curve (AUC) of 0.780 (95% CI, 0.664–0.896, p < 0.001) and 0.731 (95% CI, 0.634–0.828, p < 0.001) when using the cut-off values of 94.93 mg/L and 2.00 μg/L, respectively. However, the combined biomarker of CRP and PCT yielded a better diagnostic performance with an AUC of 0.934 (95% confidential interval (CI), 0.881–0.987, p < 0.001), which was significantly higher than that of CRP or PCT (both p < 0.001), with a sensitivity of 87.5% and a specificity of 87.3%. Our study demonstrates high levels of CRP combined with low PCT could differentiate IFI from bacterial bloodstream infections in immunocompromised children.

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Invasive Fungal Infections in Immunocompromised Children: Novel Insight Following a National Study

Cited by 14 publications

References 49 publications

Invasive fungal diseases impact on outcome of childhood ALL – an analysis of the international trial AIEOP-BFM ALL 2009

Invasive fungal diseases impact on outcome of childhood ALL – an analysis of the international trial AIEOP-BFM ALL 2009

New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study

Combination of C-Reactive Protein and Procalcitonin in Distinguishing Fungal from Bacterial Infections Early in Immunocompromised Children

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