A Retrospective Analysis of Invasive Fungal Diseases (IFD) of the Central Nervous System in Children With Lymphoid Malignancies

Abstract

Background: Outcomes of childhood hematolymphoid malignancies have improved several fold because of immunosuppressive chemotherapy and broad-spectrum antibiotics for managing febrile neutropenia. An apparent trade-off has been an increase in invasive fungal disease (IFD), affecting multiple organs. We report the diagnostic and therapeutic challenges in 8 children with lymphoid cancers who developed intracranial (IC) fungal abscesses between 2010 and 2017. Methods: Children below 15 years of age undergoing treatment for leukemia/lymphoma with clinicoradiologic and microbiologic evidence of IC fungal abscess were included. Demographic details, clinical profile, and management were retrospectively audited. Treatment was guided by European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions for IFD with therapeutic drug monitoring (TDM)-directed azole dosing, and surgical intervention. Results: Eight patients (4 B-cell acute lymphoblastic leukemia, 2 relapsed B-cell acute lymphoblastic leukemia, and 2 non-Hodgkin lymphoma) were eligible for analysis. Proven, probable, and possible IFDs were seen in 2 (25%), 4 (50%), and 2 (25%) patients, respectively. Proven IFDs were invasive mucormycosis with remaining having mold infections. Cerebrospinal fluid galactomannan was positive in all 4 patients in whom it was tested. TDM was possible in 5/8 (63%) patients. Antifungal therapy was given for a median period of 4.2 months with 5 (63%) patients having complete resolution. Three (37%) patients expired, of which 2 were attributable to IFDs. Conclusions: IC fungal abscesses in children can cause significant morbidity and mortality in children with hematolymphoid cancers. Evaluation of cerebrospinal fluid galactomannan may help in early diagnosis and therapy. Prolonged antifungal therapy steered by TDM can help achieve resolution in some cases.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study

“…Patients with acute myeloid leukemia are more prone to fungal infections. However, as more than 80% of all leukemias detected in childhood are acute lymphoblastic leukemia (ALL), and CNSFI occurs mostly in ALL cases as in our study15 and mostly during induction treatment 16. Candoni et al12 reported that CNSFI was more common in patients with ALL and in relapsed/refractory patients, 74% of the patients were neutropenic.…”

“…However, as more than 80% of all leukemias detected in childhood are acute lymphoblastic leukemia (ALL), and CNSFI occurs mostly in ALL cases as in our study 15 and mostly during induction treatment. 16 Candoni et al 12 reported that CNSFI was more common in patients with ALL and in relapsed/ refractory patients, 74% of the patients were neutropenic. In our study, most episodes (66%) occurred during the early intensification phase of the BFM ALL protocol.…”

“…Because of the location of the lesion, surgery may not always be possible. 16 In fungal lesions of the PS, surgical intervention has been reported in about 30% of the cases. 12,13 In our study, surgical intervention for the CNS lesion was done in 45% of the cases.…”

Pediatric invasive fungal rhinosinusitis

“…Diagnostic images provide an additional benefit in opportune surgical planning, evaluating orbital and central nervous system extension. Ruling out intracranial extension is critical as it is associated with a high mortality rate of 75%–100% despite radical surgery and antifungal therapy ( 21 ).…”

Antifungal Drugs TDM: Trends and Update

“…Cerebral IFI can be treated by TDM-guided azole dosing and surgical intervention and may yield improvement in some cases. 86…”