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Detection and Management of Invasive Mold Disease in Pediatric Hematological Cancer Patients
Konrad Bochennek1, Theresa Rohm1, Thomas Lehrnbecher1
1Division of Hematology, Oncology and Hemostaseology, Department of Pediatrics, Goethe University Frankfurt, Frankfurt am Main, Germany.
Abstract:
Infectious complications still remain a major challenge in the treatment of children with hematological malignancies. Invasive mold infections such as invasive aspergillosis or mucormycosis have a significant and negative impact on overall outcome in pediatric cancer patients. Although severe prolonged neutropenia is the major risk factor for invasive mold infection, other factors such as steroid exposure and acute or chronic graft-versus-host disease have to be considered in increasing the risk for infection. As clinical signs and symptoms are unspecific, diagnosis of invasive mold infection is mainly based on imaging and microbiological evaluation. Non-culture based tests using biomarkers such as galactomannan are more sensitive than culture-based tests, and there is major development of molecular techniques including next generation sequencing and analysis of cell-free DNA in order to improve both specificity and sensitivity. Antifungal strategies can be divided in prophylaxis (indicated for patients with a natural incidence of fungal infection ≥10%), empirical (eg, prolonged neutopenic fever despite broad-spectrum antibiotics) and pre-emptive therapy and treatment of established infection. Although there are exciting potent novel-class antifungal agents in the pipeline, pediatric approval of antifungal compounds significantly lags that for adult patients. To this end, despite major improvements over the last three decades, invasive mold infection is still a major challenge for pediatric patients with hematological malignancies.
Insights
Invasive mold infections pose a significant threat to children with hematological malignancies. Early diagnosis and effective antifungal strategies are crucial for improving outcomes in these vulnerable pediatric cancer patients.
Area of Science:
- Pediatric Hematology Oncology
- Infectious Diseases
- Mycology
Background:
- Infectious complications, particularly invasive mold infections (IMIs), present a major challenge in treating pediatric hematological malignancies.
- Invasive aspergillosis and mucormycosis negatively impact survival rates in pediatric cancer patients.
- Risk factors for IMIs include severe neutropenia, steroid use, and graft-versus-host disease.
Purpose of the Study:
- To review the current landscape of invasive mold infections in pediatric patients with hematological malignancies.
- To discuss diagnostic approaches, including conventional and novel biomarker-based methods.
- To outline current and emerging antifungal strategies for prophylaxis, empirical treatment, and established infections.
Main Methods:
- Review of current literature on invasive mold infections in pediatric oncology.
- Analysis of diagnostic modalities: imaging, microbiological evaluation, biomarkers (e.g., galactomannan), and molecular techniques (NGS, cfDNA).
- Categorization of antifungal strategies: prophylaxis, empirical, and pre-emptive therapy.
Main Results:
- Diagnosis relies on non-specific clinical signs, imaging, and microbiological tests, with biomarkers and molecular methods showing improved sensitivity and specificity.
- Antifungal strategies encompass prophylaxis, empirical treatment, and pre-emptive therapy.
- Despite advancements, pediatric approval for novel antifungal agents lags behind adult indications.
Conclusions:
- Invasive mold infections remain a critical challenge in pediatric hematological malignancies.
- Improved diagnostic tools and timely antifungal interventions are essential for better patient outcomes.
- Addressing the lag in pediatric antifungal drug approval is crucial for advancing care.
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