Invasive fungal disease in patients with cancer in a tertiary care pediatric hospital
Authors: Torre V , Sormani M , Esposo S , Lagala Y , Alancay A , Maydana M , Lovano F , Regalado A , Pichinenda M , Fagnani M , Ploszaj F , Uriarte V , Garcia M , Sosa F , Morales J C 
Published: October 2024

Abstract

Background
In the last two decades, the raise in invasive fungal diseases (IFD) has been associated with increased morbidity and mortality in immunosuppressed hosts. Its incidence varies between 2 to 21% and depends on the host´s underlying disease, the intensity of immunosuppressive treatment and the presence of comorbidities.
The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of IFD in patients with hematology-oncology disease.

Methods
Retrospective, descriptive study. Patients under 18 years of age with acute leukemias, lymphomas and solid tumors with a diagnosis of proven IFD (according to EORTC-MSG 2019 criteria) were included during the period from January 2020 to November 2023 in a tertiary care pediatric hospital.

Results
During the study period, 304 patients were under follow-up. 14 episodes of proven IFD were identified in 13 patients.The median age was 120 months. Male sex predominated (69.2%). The recognized factors associated were neutropenia (69.2%), use of corticosteroids in the last 3 months (61.5%) and use of previous antibiotics (92.3%). The most common underlying disease was Acute Lymphoblastic Leukemia (ALL) in 11 cases (78.5%), of which 3 were in relapse. The 21.4% of the episodes occurred in solid tumors (1 osteosarcoma of the tibia, 1 abdominal germ cell tumor, 1 neuroblastoma). Patients receiving primary prophylaxis for filamentous fungi were 3/14 (21.4%), according to the European Conference on Infections in Leukemia (ECIL-8). All received voriconazole. The fungal isolates identified were: 1 Rhizopus spp. (eye biopsy, paranasal sinuses) 1 Penicillum spp. (lung biopsy), 1 Exserohilum rostratum (skin biopsy), 1 Trichophyton asahii (blood cultures), 1 Purpuracillum lilacinus (skin biopsy), 1 Aspergillus fumigatus (Bronchoalveolar lavage, BAL),: 3 Candida parapsilosis (blood cultures), 1 Candida tropicalis (blood cultures), 1 Candida spp (blood cultures), 1 Malassezia (BAL). The patients with invasive molds infections were six, all of them with pathological chest tomography. Galactomannans (GM) were positive in 66% (4/6). BAL with positive GM was performed in 2 of them. The primary focus were: cutaneous (3/6), pulmonary (2/6) and orbital-rhinosinusal (1/6). Regarding IFD due to yeast fungi: all Candida infections were associated with central venous catheters fungemia. Malassezia infection presented with pulmonary involvement. Fungal co-infection was observed in 1 patient with documentation of Aspergillus fumigatus in BAL and Candida tropicalis in blood and urine cultures.
Empirical antifungal therapy was liposomal amphotericin in 76.9 % of the patients. Two patients died (15.4%) at 30 days of follow-up.

Conclusion
Early diagnosis and timely antifungal therapy represent the main strategies to increase the survival of patients with IFD. Antifungal prophylaxis is postulated as an effective prevention measure and its indication should be defined according to the patient’s characteristics and the incidence of IFD at the treating center.
We consider that patients with suspected IFD and clinical focus should undergo the corresponding tissue biopsy for culture, histological evaluation, and molecular biology, to direct the appropriate treatment.
Candida species represent the most frequent isolates, however, Aspergillus and Rhizopus infections are associated with higher morbidity and mortality.