Hepatosplenic Fungal Infections in Children With Leukemia—Risk Factors and Outcome: A Multicentric Study

Çelkan, Tiraje; Kizilocak, Hande; Evim, Melike Sezgin; Güneş, Adalet Meral; Özbek, Namık; Yaralı, Neşe; Ünal, Ekrem; Patıroğlu, Türkan; Karapınar, Deniz Yılmaz; Sarper, Nazan; Zengin, Emine; Karaman, Serap; Koçak, Ülker; Kürekçi, Emin; Özdemir, Canan; Tuğcu, Deniz; Uysalol, Ezgi; Dikme, Gürcan; Adaletli, İbrahim; Kuruoğlu, Sebuh; Kebudi, Rejin

doi:10.1097/mph.0000000000001431

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…were isolated from blood cultures in 30% of those cases. Celkan et al [ 29 ], in a multicentric study from Turkey, recently reported that 8 out of 40 (22.5%) children with HSC had Candida spp. and only one case was C. albicans.…”

Section: Discussionmentioning

confidence: 99%

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

Evim

Tüfekçi

Baytan

et al. 2021

Tjh

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Objective: The incidence of invasive fungal infections (IFIs) has increased due to intensive chemotherapy in childhood leukemia. The aim of this study was to evaluate the incidence, risk factors, causative pathogens, and impact on survival of IFIs among pediatric leukemia patients. Materials and Methods: The hospital records of 307 children with acute lymphoblastic leukemia (ALL, n=238), acute myeloid leukemia (AML, n=51), and relapsed leukemia (n=18) between January 2010 and December 2015 were retrospectively evaluated. Results: A total of 1213 febrile neutropenia episodes were recorded and 127 (10.4%) of them were related to an IFI. Of 307 children, 121 (39.4%) developed IFIs. The mean age was significantly older in the IFI group compared to children without IFIs (p<0.001). IFIs were defined as possible, probable, and proven in 73.2%, 11.9%, and 14.9% of the attacks, respectively. Invasive aspergillosis (81.9%) was the most frequent infection, followed by invasive candidiasis (13.4%) and rare fungal diseases (4.8%). The majority of IFI attacks in both ALL and AML occurred during the induction phase. In total, the death rate was 24% and the IFI-related mortality rate was 18%. The mortality rate among children with IFIs was found to be significantly higher than that of children without IFIs (p<0.001). Overall and event-free survival rates at 5 years were also found to be significantly lower in the IFI group (p<0.001). Relapse (odds ratio: 8.49) was the most effective risk factor for mortality, followed by developing an IFI episode (odds ratio: 3.2) and AML (odds ratio: 2.33) according to multivariate regression analysis. Conclusion: Our data showed that IFIs were more common in older children. Although proven and probable IFI episodes were more frequently diagnosed in cases of relapse and AML, children with ALL and AML had similar frequencies of experiencing at least one episode of IFI. Rare fungal diseases were also identified as a major problem. Despite success in treatment, IFIs increased the rate of mortality in children with acute leukemia.

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Section: Discussionmentioning

confidence: 99%

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

Evim

Tüfekçi

Baytan

et al. 2021

Tjh

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“…In children, the incidence of invasive fungal infection is reported to be 9%‐10% with mortality rates ranging from 21% to 48% . However, HSFI is rare in children with leukaemia, and the incidence of HSFI is not known. Risk factors for invasive candidiasis in patients with haematological malignancies include neutropenia, corticosteroid therapy, mucositis and the presence of central venous catheters …”

Section: Introductionmentioning

confidence: 99%

Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies

Madney

Shalaby

Elanany

et al. 2019

Mycoses

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Summary Hepatosplenic fungal infection (HSFI) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukaemia treated with intensive chemotherapy. Retrospective analysis including all paediatric haematological malignancies patients with HSC treated in Children Cancer Hospital Egypt (2013‐2018). Twenty‐five patients with acute leukaemia developed HSFI (19 patients diagnosed as hepatosplenic candidiasis). Most of the cases (92%) occurred during the induction phase. Organs affected were as follows: liver in 18 patients, renal in 13 patients, spleen in 12 patients, skin in four patients and retina in one patient. Five (20%) patients had proven HSC, 14 (56%) probable and six (24%) possible HSFI. Ten patients had a PET‐CT for response assessment. Candida tropicalis was the most common isolated spp. from blood/tissue culture. Six (24%) patients developed HSFI on top of antifungal prophylaxis. Steroids were given in 12 (52%) patients with HSFI as immune reconstitution syndrome (IRS). Caspofungin was the first line of treatment in 14 (56%) patients, liposomal amphotericin B in six (24%) patients and azoles in five (20%) patients. HSFI was associated with delayed of intensification phase of chemotherapy (median 42 days). The success rate was reported in 24 patients with complete response (68%) and partial response in (28%) patients, while failure (death) seen in 1(4%) patient. HSC is still a major challenge in paediatric leukaemias patients with impact on treatment delay and survival outcome. PET scan, non‐culture diagnostics and steroid role evidence in IRS are growing. Antifungal stewardship for screening, early detection for high‐risk patients and better response assessment is challenging.

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“…CNSFI was most commonly accompanied by lung involvement, followed by paranasal IFI in our patients. In our recently published study, in 40 children with leukemia and hepatosplenic fungal infection, 57% were accompanied by fungal infection in other regions, most commonly the lungs 31…”

Section: Discussionmentioning

confidence: 89%

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

Karaman

Kebudi

Kizilocak

et al. 2022

Journal of Pediatric Hematology/Oncology

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Background: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. Materials and Methods: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541). Results: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus. Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. Conclusion: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

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Hepatosplenic Fungal Infections in Children With Leukemia—Risk Factors and Outcome: A Multicentric Study

Cited by 11 publications

References 31 publications

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

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

Clinical features and outcome of hepatosplenic fungal infections in children with haematological malignancies

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

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