Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia

Colombo, Arnaldo Lopes; Bergamasco, Maria Daniela; Nouér, Simone Aranha; Castro, Paulo de Tarso Oliveira e; Pasqualotto, Alessandro C.; Queiroz‐Telles, Flávio; Abdala, Edson; Ramos, Jéssica Fernandes; Falci, Diego Rodrigues; Nucci, Márcio

doi:10.1007/s11046-022-00684-z

Cited by 2 publications

(2 citation statements)

References 25 publications

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“…Authors relate an incidence of between 2.2% and 15.4% of IMD, IA being the most frequent [ 26 , 27 ]. Interestingly, ALL patients seem less prone to pulmonary forms of IA, with more rhino-sinusal infections [ 28 ]. Relapsed or refractory disease is associated with a higher risk of IA, with an incidence of 23.5% compared to 6.2% in a pediatric series and 28.5% vs 5.6% in adult patients: of note, the chemotherapy in this setting tends to resemble that of AML [ 27 , 29 ].…”

Section: Patientsmentioning

confidence: 99%

Invasive Pulmonary Aspergillosis

Ledoux

Herbrecht

2023

JoF

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Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.

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Section: Patientsmentioning

confidence: 99%

Invasive Pulmonary Aspergillosis

Ledoux

Herbrecht

2023

JoF

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“…causes a spectrum of diseases, including asthma, chronic infection, and invasive disease. Invasive fungal infections carry elevated mortality rates in these high-risk patients, despite the availability of antifungals (1)(2)(3)(4), demonstrating the critical role of the innate immune system as the first line of defense against these devastating infections (5,6).…”

Section: Introductionmentioning

confidence: 99%

BTK inhibitor–induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α

Vargas-Blanco,

Hepworth,

Basham

et al. 2024

JCI Insight

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Inhibition of Bruton’s tyrosine kinase (BTK) through covalent modifications of its active site (e.g. , ibrutinib [IBT]) is a preferred treatment for multiple B cell malignancies. However, IBT-treated patients are more susceptible to invasive fungal infections, although the mechanism is poorly understood. Neutrophils are the primary line of defense against these infections; therefore, we examined the effect of IBT on primary human neutrophil effector activity against Aspergillus fumigatus . IBT significantly impaired the ability of neutrophils to kill A . fumigatus and potently inhibited reactive oxygen species (ROS) production, chemotaxis, and phagocytosis. Importantly, exogenous TNF-α fully compensated for defects imposed by IBT and newer-generation BTK inhibitors and restored the ability of neutrophils to contain A . fumigatus hyphal growth. Blocking TNF-α did not affect ROS production in healthy neutrophils but prevented exogenous TNF-α from rescuing the phenotype of IBT-treated neutrophils. The restorative capacity of TNF-α was independent of transcription. Moreover, the addition of TNF-α immediately rescued ROS production in IBT-treated neutrophils, indicating that TNF-α worked through a BTK-independent signaling pathway. Finally, TNF-α restored effector activity of primary neutrophils from patients on IBT therapy. Altogether, our data indicate that TNF-α rescued the antifungal immunity block imposed by inhibition of BTK in primary human neutrophils.

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Invasive Aspergillosis in Patients with Acute Leukemia: Comparison Between Acute Myeloid and Acute Lymphoid Leukemia

Cited by 2 publications

References 25 publications

Invasive Pulmonary Aspergillosis

Invasive Pulmonary Aspergillosis

BTK inhibitor–induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α

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