Frequency and Determinants of Invasive Fungal Infections in Children With Solid and Hematologic Malignancies in a Nonallogeneic Stem Cell Transplantation Setting: A Narrative Review

Abstract

Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in children with cancer. An overview of studies on the frequency and determinants of IFI in pediatric oncology patients in nonallogeneic stem cell transplantation settings is lacking. We performed a literature review in Pubmed and Embase, and included 13 prospective and 23 retrospective studies. The IFI frequency (proven/probable based on EORTC criteria) in nonallogeneic stem cell transplantation pediatric cancer patients ranged between 1.0% and 38.0%, with the highest frequencies reported in hematologic malignancies. The most common fungal species seen in the studied population was Candida, followed by Aspergillus. IFI are not well investigated in solid tumor patients. Significant recurrent determinants from univariate analysis were the diagnosis acute myeloid leukemia, (prolonged) neutropenia and an older age (above 10 years). The only 2 significant determinants based on multivariate analysis were the preceding number of days of broad-spectrum antibiotics (odds ratio, 1.05; 95% confidence interval, 1.02-1.07; P=0.0006) and the number of days of corticosteroids (odds ratio, 1.05; 95% confidence interval, 1.02-1.09; P=0.005), that were both based on a group of acute myeloid leukemia patients only. Future studies are necessary to determine the frequency and determinants of IFI in pediatric oncology including a representative number of solid tumor patients.

Invasive Fungal Infections in Children with Leukemia: The Clinical Features and Prognosis

“…We found that children with ALL and AML had a similar frequency of experiencing at least one episode of IFI. This finding is contrary to the previous data in the literature suggesting that the frequency of IFI episodes in AML is higher than that in ALL [ 4 , 19 ]. The prevalence of IFI in ALL is reported to be between 4% and 35% depending on the era, chemotherapy protocol, risk categories, and antifungal prophylaxis [ 6 , 7 , 12 , 17 , 20 , 21 , 22 ].…”

“…In the current study, the incidence of IFI episodes was found to be 10.4%. The incidence in cases of hematologic malignancies ranged between 1.7% and 35.4% in various studies [ 4 , 9 , 10 , 11 , 12 ]. However, it may increase further in autopsy findings [ 13 ].…”

“…The mean age in the IFI group was significantly higher compared to children in the non-IFI group. The incidence of IFIs is reported to increase with age [ 4 , 7 , 17 ]. This finding could be attributed to the fact that colonization is less frequent in the younger population due to less contact with fungal spores and the lower frequency of unfavorable genetic mutations [ 1 , 18 ].…”

“…However, invasive fungal infections (IFIs) are still a significant cause of mortality and morbidity in children with hematologic malignancies [ 3 ]. It is hard to estimate the true incidence of IFIs, but it has been increasing in recent years due to advances in diagnostic methods, the use of intensive chemotherapy, prolonged neutropenia, and the increased use of central catheters [ 3 , 4 ]. Although new antifungals are available, IFI-related mortality still remains high, reported to be between 20% and 70% in various studies [ 4 , 5 , 6 , 7 , 8 ].…”

Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

“…Intensified anticancer treatment is now increasingly used even in elderly patients; this is true even for the most aggressive diseases requiring very intensive treatment like allogeneic stem cell transplantation [ 74 ]. Intensified treatment will usually increase the risk of severe neutropenia and such severely immunocompromised patients are prone to a wide range of viral, bacterial, and fungal infections [ 117 , 118 , 119 , 120 , 121 , 122 ]. CRP levels can be used for the evaluation of anti-infectious treatment.…”