Breakthrough Invasive Fungal Infections in Pediatric Acute Myeloid and Lymphoblastic Leukemia Receiving Mold-active

Belgin Gülhan1, Fatma Ünal2, Özlem Arman3

  • 1From the Pediatric Infectious Disease Department, Ankara Bilkent Children City Hospital, University of Health Science.

Abstract

Insights

Despite antifungal prophylaxis, nearly one-third of pediatric leukemia patients developed invasive fungal infections (IFIs). High mortality rates in probable and proven IFIs highlight limitations in current strategies for these vulnerable children.

Area of Science:

  • Pediatric Hematology
  • Infectious Diseases
  • Oncology

Background:

  • Breakthrough invasive fungal infections (IFIs) are a significant challenge in pediatric acute leukemia patients, even with antifungal prophylaxis.
  • Limited data exists on the epidemiology, risk factors, and outcomes of IFIs in this population.

Purpose of the Study:

  • To investigate the incidence, characteristics, and outcomes of breakthrough IFIs in children with acute leukemia receiving mold-active antifungal prophylaxis.
  • To evaluate the effectiveness of current prophylactic strategies and identify areas for improvement.

Main Methods:

  • Retrospective cohort study of 147 pediatric acute leukemia patients (0-18 years) treated between February 2019 and December 2023.
  • Analysis of demographic and clinical features, antifungal prophylaxis regimens, IFI classification (EORTC/MSGERC 2020 criteria), microbiological and radiological findings, and outcomes.
  • Patients received mold-active antifungal prophylaxis, primarily voriconazole.

Main Results:

  • Overall, 29.3% of patients developed IFIs, with similar incidence in acute lymphoblastic leukemia (29.0%) and acute myeloid leukemia (31.2%).
  • Most IFIs were classified as possible (81.4%), with lower proportions of probable (11.6%) and proven (7.0%) cases.
  • A case-fatality rate of 16.3% (7/43) was observed among patients with IFIs, with significantly higher mortality in probable (60.0%) and proven (66.7%) infections compared to possible infections (5.7%).

Conclusions:

  • Nearly one-third of pediatric leukemia patients developed IFIs despite mold-active prophylaxis, indicating limitations in current prophylactic strategies.
  • High mortality associated with probable and proven IFIs necessitates improved diagnostic approaches and optimized prophylactic regimens.
  • Further research is needed to enhance therapeutic drug monitoring and early diagnostic methods to reduce IFI burden in high-risk pediatric leukemia patients.