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Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review)

  • Authors:
    • Mingxin He
    • Feng Chen
    • Xiaomin Xian
    • Zhi Guo
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Affiliated Nanshan Hospital of Shenzhen University, Shenzhen, Guangdong 518052, P.R. China, Oncology Center, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, P.R. China, National Cancer Center/National Clinical Research Center for Cancer, Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong 518116, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 21
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    Published online on: November 14, 2025
       https://doi.org/10.3892/etm.2025.13016
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Abstract

Invasive fungal disease (IFD) has a high incidence rate in pediatric patients with hematological malignancies and hematopoietic stem cell transplantation, markedly elevating mortality rates. Major pathogens include Aspergillus, Candida and emerging non‑Aspergillus molds. Clinical manifestations such as persistent fever and dyspnea are frequently non‑specific, complicating early diagnosis. Invasive candidiasis typically manifests as candidemia or hepatosplenic infection, whereas invasive aspergillosis predominantly involves the lower respiratory tract. Prophylactic antifungal therapy reduces IFD risk but may lead to breakthrough IFD, particularly during prolonged neutropenia (>14 days). Treatment strategies require individualized selection between monotherapy and combination regimens, incorporating patient status, local epidemiology, prior antifungal exposure, drug metabolism and socioeconomic factors; however, treatment strategies can be hindered by diagnostic challenges including age‑specific biomarker thresholds. Emerging techniques such as metagenomic next‑generation sequencing show promise for rapid pathogen identification. Central nervous system involvement occurs in a certain proportion of pediatric cases and requires multimodal intervention. Early diagnosis through optimized imaging and timely initiation of targeted therapy are key to overcome clinical challenges and improving prognosis in this vulnerable population. The present review aimed to systematically review the epidemiological characteristics, diagnostic challenges and therapeutic strategies of IFD in pediatric hematological malignancies post‑chemotherapy. By collating current clinical evidence, the present review provides an evidence‑based framework for optimizing management in this high‑risk population.
View Figures

Figure 1

Activation of innate and adaptive
immunity against fungal pathogens.. Fungal infections (such as
Aspergillus and Candida) activate the innate immune
system through PRRs that recognize pathogen-associated molecular
patterns. PRRs are primarily expressed on APCs such as dendritic
cells and macrophages. Fungal infections activate neutrophils,
monocytes, macrophages and dendritic cells in the intrinsic immune
system, which in turn stimulate the adaptive immune system. PRRs,
pattern recognition receptors; APCs, antigen-presenting cells; Th,
T helper cell.

Figure 2

Schematic representation of B-cell
differentiation. The process begins in the bone marrow with
hematopoietic stem cells, which undergo a series of differentiation
steps to become immature B cells. This antigen-independent phase
involves the rearrangement and expression of immunoglobulin genes.
Upon encountering a specific antigen in the periphery, mature B
cells are activated, proliferate and undergo clonal expansion.
These activated B cells finally differentiate into
antibody-secreting plasma cells, which mediate humoral immunity,
and long-lived memory B cells, which provide lasting immunological
protection.

Figure 3

Mechanisms of the innate and adaptive
immune response to invasive fungal disease. Antigen-presenting
cells recognize the fungus via protease-associated receptors, which
can release pro-inflammatory cytokines to act on T cells. A T
helper 1 response occurs to promote the release of g-interferon to
act on macrophages, which collectively mediate phagocytosis and
fungal killing.
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Spandidos Publications style
He M, Chen F, Xian X and Guo Z: Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review). Exp Ther Med 31: 21, 2026.
APA
He, M., Chen, F., Xian, X., & Guo, Z. (2026). Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review). Experimental and Therapeutic Medicine, 31, 21. https://doi.org/10.3892/etm.2025.13016
MLA
He, M., Chen, F., Xian, X., Guo, Z."Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review)". Experimental and Therapeutic Medicine 31.1 (2026): 21.
Chicago
He, M., Chen, F., Xian, X., Guo, Z."Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review)". Experimental and Therapeutic Medicine 31, no. 1 (2026): 21. https://doi.org/10.3892/etm.2025.13016
Copy and paste a formatted citation
x
Spandidos Publications style
He M, Chen F, Xian X and Guo Z: Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review). Exp Ther Med 31: 21, 2026.
APA
He, M., Chen, F., Xian, X., & Guo, Z. (2026). Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review). Experimental and Therapeutic Medicine, 31, 21. https://doi.org/10.3892/etm.2025.13016
MLA
He, M., Chen, F., Xian, X., Guo, Z."Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review)". Experimental and Therapeutic Medicine 31.1 (2026): 21.
Chicago
He, M., Chen, F., Xian, X., Guo, Z."Diagnosis and treatment of invasive fungal disease in children with hematological malignancies after chemotherapy: Challenges and strategies (Review)". Experimental and Therapeutic Medicine 31, no. 1 (2026): 21. https://doi.org/10.3892/etm.2025.13016
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