{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:25:43Z","timestamp":1784917543329,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016\u20132021) and assessed factors associated with proven\/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven\/probable IFI (11 yeast; eight molds). The proven\/probable yeast IFI rate was 6\/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5\/41 (12.2%) in the non-HR-IFI-AL category (standard\/intermediate risk ALL). The proven\/probable mold IFI rate was 7\/52 (13.5%) in HR-IFI-AL children and 1\/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven\/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven\/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly.<\/jats:p>","DOI":"10.3390\/microorganisms12010145","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T05:24:12Z","timestamp":1704950652000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Invasive Fungal Infections in Children with Acute Leukemia: Epidemiology, Risk Factors, and Outcome"],"prefix":"10.3390","volume":"12","author":[{"given":"Tamar Ruth","family":"Gal Etzioni","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit","family":"Fainshtain","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Nitzan-Luques","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigal","family":"Weinreb","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"The Dyna & Fala Weinstock Department of Pediatric Hematology Oncology, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Temper","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3276-0963","authenticated-orcid":false,"given":"Maya","family":"Korem","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Department of Microbiology and Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Averbuch","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel"},{"name":"Pediatric Division, Hadassah Medical Center, Jerusalem 91120, Israel"},{"name":"Pediatric Infectious Diseases, Hadassah Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1470-2045(14)70017-8","article-title":"Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation","volume":"15","author":"Groll","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/ejh.12910","article-title":"Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high-risk pediatric onco-hematological patients","volume":"99","author":"Cesaro","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1097\/INF.0000000000002010","article-title":"Risk Factors for Invasive Fungal Infection in Children and Adolescents with Hematologic and Malignant Diseases: A 10-year Analysis in a Single Institute in Japan","volume":"37","author":"Kobayashi","year":"2018","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1097\/MPH.0b013e3181864a80","article-title":"The clinical feature of invasive fungal infection in pediatric patients with hematologic and malignant diseases: A 10-year analysis at a single institution at Japan","volume":"30","author":"Kobayashi","year":"2008","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lehrnbecher, T., Sch\u00c3\u00b6ning, S., Poyer, F., Georg, J., Becker, A., Gordon, K., Attarbaschi, A., and Groll, A.H. (2019). Incidence and Outcome of Invasive Fungal Diseases in Children with Hematological Malignancies and\/or Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Multicenter Study. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00681"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/pbc.23005","article-title":"Invasive fungal infections in pediatric oncology","volume":"56","author":"Mor","year":"2011","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/01.mph.0000155861.38641.ca","article-title":"Invasive fungal infections in pediatric oncology patients: 11-year experience at a single institution","volume":"27","author":"Rosen","year":"2005","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_8","first-page":"94","article-title":"Invasive Fungal Infections in Children with Leukemia: Clinical Features and Prognosis","volume":"39","author":"Baytan","year":"2022","journal-title":"Turk. J. Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1200\/JCO.2016.71.7017","article-title":"Guideline for the Management of Fever and Neutropenia in Children with Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update","volume":"35","author":"Lehrnbecher","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1586\/ehm.12.53","article-title":"Diagnostic methods for invasive fungal diseases in patients with hematologic malignancies","volume":"5","author":"Riwes","year":"2012","journal-title":"Expert. Rev. Hematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/jac\/dkp507","article-title":"Overall survival and fungal infection-related mortality in patients with invasive fungal infection and neutropenia after myelosuppressive chemotherapy in a tertiary care centre from 1995 to 2006","volume":"65","author":"Glasmacher","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and Update of the Consensus Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S2352-4642(19)30191-9","article-title":"Pre-emptive versus empirical antifungal therapy in immunocompromised children","volume":"3","author":"Lehrnbecher","year":"2019","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/cid\/ciq147","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","unstructured":"Martin, S. (2017). Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia\u2014AIEOP-BFM ALL 2017."},{"key":"ref_16","unstructured":"Abrahamsson, J. (2024, January 08). Research Study for Treatment of Children and Adolescents with Acute Myeloid Leukaemia 0\u201318 Years (AML2012), Available online: https:\/\/www.clinicaltrials.gov\/study\/NCT01828489."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e254","DOI":"10.1016\/S1470-2045(20)30723-3","article-title":"8th European Conference on Infections in Leukaemia: 2020 guidelines for the diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or post-haematopoietic cell transplantation","volume":"22","author":"Groll","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"Walsh","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/s41375-022-01768-x","article-title":"Invasive fungal diseases impact on outcome of childhood ALL\u2014An analysis of the international trial AIEOP-BFM ALL 2009","volume":"37","author":"Lehrnbecher","year":"2023","journal-title":"Leukemia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1056\/NEJMoa061094","article-title":"Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia","volume":"356","author":"Cornely","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1001\/jama.2019.15702","article-title":"Effect of Caspofungin vs Fluconazole Prophylaxis on Invasive Fungal Disease Among Children and Young Adults with Acute Myeloid Leukemia: A Randomized Clinical Trial","volume":"322","author":"Fisher","year":"2019","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2860","DOI":"10.1093\/jac\/dky244","article-title":"Efficacy of pre-emptive versus empirical antifungal therapy in children with cancer and high-risk febrile neutropenia: A randomized clinical trial","volume":"73","author":"Santolaya","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/cid\/ciac623","article-title":"Empiric vs Preemptive Antifungal Strategy in High-Risk Neutropenic Patients on Fluconazole Prophylaxis: A Randomized Trial of the European Organization for Research and Treatment of Cancer","volume":"76","author":"Maertens","year":"2023","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e29275","DOI":"10.1002\/pbc.29275","article-title":"Invasive fungal disease in children with acute myeloid leukaemia: An Australian multicentre 10-year review","volume":"68","author":"Yeoh","year":"2021","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Douglas, A.P., Stewart, A.G., Halliday, C.L., and Chen, S.C. (2023). Outbreaks of Fungal Infections in Hospitals: Epidemiology, Detection, and Management. J. Fungi, 9.","DOI":"10.3390\/jof9111059"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.jiac.2019.04.005","article-title":"Infectious profile in children with ALL during chemotherapy: A report of study group for infections","volume":"25","author":"Zawitkowska","year":"2019","journal-title":"J. Infect. Chemother. Off. J. Jpn. Soc. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1111\/myc.12303","article-title":"Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: Results from an university hospital, 2005\u20132013","volume":"58","author":"Karadas","year":"2015","journal-title":"Mycoses"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1182\/blood-2003-10-3446","article-title":"Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: A Children\u2019s Cancer Group study","volume":"106","author":"Whitlock","year":"2005","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/sj.leu.2400989","article-title":"Down\u2019s syndrome in childhood acute lymphoblastic leukemia: Clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group","volume":"12","author":"Dordelmann","year":"1998","journal-title":"Leukemia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"myac010","DOI":"10.1093\/mmy\/myac010","article-title":"Clinical characteristics and outcome of invasive fungal sinusitis in children with hematological malignancies","volume":"60","author":"Eissa","year":"2022","journal-title":"Med. Mycol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/pbc.20717","article-title":"Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders","volume":"48","author":"Hovi","year":"2007","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/bjh.15798","article-title":"The incidence of invasive fungal infections in children, adolescents and young adults with acute lymphoblastic leukaemia\/lymphoma treated with the UKALL2011 protocol: A multicentre retrospective study","volume":"186","author":"Govender","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_33","unstructured":"Baggott, C., Fochtman, D., Foley, G., and Patterson Kelly, K. (2011). Nursing Care of Children and Adolsecents with Cancer and Blood Disorders, APHON. [4th ed.]."},{"key":"ref_34","unstructured":"Scammon, R.E. (1930). The Measurement of Man, Harris, J.A., Jackson, C.M., Paterson, D.G., Scammon, R.E., Eds., University of Minnesota Press."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/sj.bmt.1703172","article-title":"Infections after stem cell transplantation in children: State of the art and recommendations","volume":"28","author":"Dini","year":"2001","journal-title":"Bone Marrow Transplant."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/1\/145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:44:33Z","timestamp":1760103873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/1\/145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["microorganisms12010145"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12010145","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,11]]}}}