Summary of Guidelines for the Diagnosis, Prevention, and Treatment of Invasive Fungal Infections in Pediatric Patients with Leukemia and Post Hematopoietic Stem Cell Transplantation

Introduction

Although pediatric hemato-oncology patients are susceptible to fungal infections similarly to adult patients, there are several relevant differences in the biology and treatment of underlying diseases and age-related comorbidities between these two groups. Therefore, the first international recommendations for the diagnosis, prevention, and treatment of invasive fungal infections in pediatric patients were created in 2011 and reviewed and updated in 2020. The summary of the recent guidelines presents recommendations with the highest strength of recommendation class A and B.

Recommendations for the diagnosis of invasive fungal infections

Prospective monitoring of galactomannan in serum 2 times a week for the early diagnosis of invasive aspergillosis (class A) is recommended for high-risk patients without active prophylaxis. Detection of galactomannan in serum is also useful in patients with prolonged febrile neutropenia and/or abnormalities on CT scans (class A). An optical density index value of ≥ 0.5 is considered the threshold for a positive galactomannan result in serum (class B).

A complementary tool for diagnosing invasive pulmonary aspergillosis is galactomannan detection from bronchoalveolar lavage with a positivity threshold of ≥ 1 (class A). For diagnosing invasive aspergillosis in the central nervous system, galactomannan detection from cerebrospinal fluid with a positivity threshold of ≥ 1 is possible (class A).

Nucleic acid detection (PCR diagnostics) is recommended for diagnostic purposes from plasma, serum, or blood samples (class B). Its use in samples obtained from bronchoalveolar lavage, cerebrospinal fluid, body fluids, and tissue samples is recommended whenever these samples are available (class A).

A high-resolution chest computed tomography (HRCT) scan should be performed in high-risk patients with febrile neutropenia persisting for more than 96 hours or with suspicious clinical findings (class A). The presence of typical and atypical lung infiltrates may indicate invasive fungal infection and should lead to the acceleration of the diagnostic process and initiation of antifungal therapy (class A). CT scans of paranasal sinuses should be performed only in patients with local symptoms (class B). In patients with proven pulmonary fungal infection, imaging of the head (ideally with magnetic resonance imaging) should be considered even in the absence of neurological symptoms (class B).

Recommendations for the prevention and treatment of invasive fungal infections

Primary antifungal prophylaxis is strongly recommended in patients at high risk of invasive fungal infections (class A). In primary chemoprophylaxis, the highest recommendation strength is for administering fluconazole (in patients with leukemia and in the pre-hematopoietic stem cell transplantation phase, not in the post-transplantation phase) and posaconazole. A class B recommendation was achieved for itraconazole, liposomal amphotericin B, and voriconazole. Empirical antifungal therapy, if chosen, should be initiated in high-risk patients with granulocytopenia and fever of unknown origin lasting more than 96 hours and not responding to broad-spectrum antibiotics (class B).

In the treatment of invasive candidiasis, the highest class recommendations are for administering caspofungin, liposomal amphotericin B, micafungin, and anidulafungin (a class B recommendation for administering voriconazole and fluconazole). In the treatment of invasive aspergillosis, the highest class recommendations are for administering voriconazole and isavuconazole (a class B recommendation for administering liposomal amphotericin B). In the treatment of mucormycosis, a class A recommendation is for administering liposomal amphotericin B.

Conclusion

During the European ECIL-8 conference, the recommendations for diagnosing, preventing, and treating invasive fungal infections in pediatric patients were revised and updated based on the results of current clinical studies.

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Source: Groll A. H., Pana D., Lanternier F. et al.; 8^th European Conference on Infections in Leukemia. 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in pediatric patients with cancer or post-hematopoietic cell transplantation. Lancet Oncol 2021; 22 (6): e254–e269, doi: 10.1016/S1470-2045(20)30723-3.