{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:28:51Z","timestamp":1786786131036,"version":"build-2736575974"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":56,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003010","name":"Ege University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003010","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acquired aplastic anemia (AA) is a life-threatening bone marrow failure disorder, and febrile neutropenia (FN) episodes in children with AA pose significant risks due to infections. The study aimed to investigate the incidence, types, and outcomes of infections during FN episodes in pediatric AA patients.\u00a0This single-centre retrospective cohort study included 39 pediatric patients with AA diagnosed between January 2004 and January 2024. Data from medical records, including clinical characteristics, laboratory findings, immunosuppressive therapy details, microbiological results, and infection outcomes, were analyzed. Infection sources, pathogens, and outcomes were assessed, and statistical analysis was performed to identify risk factors for infections and mortality.\u00a0Twenty-five patients were male (64.1%), with a median age of 12,05 years (interquartile range : 6 to 14,94y). A total of 152 FN episodes were evaluated, with 87.1% of patients experiencing at least one episode [median, 4.15 (range:1\u201315)]. 58 (38.1%) episodes were classified as microbiologically documented infections(MDI); bloodstream infections(BSIs) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200936, 23.6%) were the most common, including central line-associated BSIs (CLABSIs) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200929, 19%). Among BSIs, 81% (29\/36) were caused by Gram-negative (GN) bacteria and 19% (7\/36) by Gram-positive (GP) bacteria. The most frequently isolated microorganism was coagulase-negative\n                    <jats:italic>Staphylococci<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200913, 8.55%), followed by\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912, 7.89%) with a high extended-spectrum beta-lactamase (ESBL) positivity rate (69%). Fungal infections (proven+probable) were identified in 8 episodes (5.26%), and viral infections in 3 episodes (1.97%). Rabbit-derived antithymocyte globulin (RD-ATG ) was found to be significantly associated with BSIs in both univariable and logistic regression analyses (OR 8.8, 95% CI 1.692\u201345.761,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006). The attributable mortality (AM) of infection episodes was 5.2%. In multivariate analysis, bacterial BSIs, particularly GN- BSIs and those receiving RD-ATG, were significant predictors of increased mortality (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). GN bacterial infections and fungal infections negatively affected survival.\u00a0RD-ATG therapy was identified as a risk factor for increased infection frequency and severity, particularly in cases of BSIs and GN bacteremia. Timely and appropriate antimicrobial treatment is crucial, and the high mortality rates associated with severe infections underscore the importance of early detection and intervention.\n                  <\/jats:p>","DOI":"10.1007\/s00277-026-06874-9","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T07:35:00Z","timestamp":1779694500000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Febrile neutropenia in pediatric acquired aplastic anemia: a 20-year analysis of infections and mortality"],"prefix":"10.1007","volume":"105","author":[{"given":"Gulhadiye","family":"Avcu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal","family":"Karadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysha","family":"Gadashova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cihan","family":"Onder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli","family":"Arslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zumrut Sahbudak","family":"Bal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohret","family":"Aydemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek Yesim","family":"Metin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz Yilmaz","family":"Karapinar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"issue":"6","key":"6874_CR1","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1111\/j.1600-0609.2012.01770.x","volume":"88","author":"P Quarello","year":"2012","unstructured":"Quarello P, Saracco P, Giacchino M, Caselli D, Caviglia I, Longoni D, Varotto S, Rana I, Amendola A, Misuraca A, Licciardello M, Paolucci P, Ladogana S, Rivetti E, Dufour C, Castagnola E (2012) Epidemiology of infections in children with acquired aplastic anaemia: a retrospective multicenter study in Italy. Eur J Haematol 88(6):526\u2013534","journal-title":"Eur J Haematol"},{"key":"6874_CR2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3324\/haematol.11107","volume":"92","author":"JC Marsh","year":"2007","unstructured":"Marsh JC (2007) Treatment of acquired aplastic anemia. Haematologica 92:2\u20135","journal-title":"Haematologica"},{"key":"6874_CR3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.hoc.2009.01.011","volume":"23","author":"EC Guinan","year":"2009","unstructured":"Guinan EC (2009) Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am 23:171\u2013191","journal-title":"Hematol Oncol Clin North Am"},{"key":"6874_CR4","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/j.1365-2141.2007.06903.x","volume":"140","author":"P Saracco","year":"2008","unstructured":"Saracco P, Quarello P, Iori AP et al (2008) Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long-term observation follow-up. Br J Haematol 140:197\u2013205","journal-title":"Br J Haematol"},{"key":"6874_CR5","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1016\/S0889-8588(18)30225-9","volume":"7","author":"M Weinberger","year":"1993","unstructured":"Weinberger M (1993) Approach to the management of fever and infection in patients with primary bone marrow failure and hemoglobinopathies. Hematol Oncol Clin North Am 7:865","journal-title":"Hematol Oncol Clin North Am"},{"key":"6874_CR6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.7017","volume":"35","author":"T Lehrnbecher","year":"2017","unstructured":"Lehrnbecher T, Robinson P, Fisher B et al (2017) Guideline for the management of fever and neutropenia in children with cancer and hematopoietic stem-cell transplantation recipients: 2017 update. J Clin Oncol 35:2082","journal-title":"J Clin Oncol"},{"key":"6874_CR7","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1002\/cncr.11478","volume":"98","author":"HA Torres","year":"2003","unstructured":"Torres HA, Bodey GP, Rolston KV et al (2003) Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Cancer 98:86","journal-title":"Cancer"},{"key":"6874_CR8","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciq245","volume":"52","author":"JM Valdez","year":"2011","unstructured":"Valdez JM, Scheinberg P, Nunez O et al (2011) Decreased infection-related mortality and improved survival in severe aplastic anemia in the past two decades. Clin Infect Dis 52:726","journal-title":"Clin Infect Dis"},{"issue":"3","key":"6874_CR9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1097\/MPH.0000000000001631","volume":"42","author":"A Samanta","year":"2020","unstructured":"Samanta A, Chandra J, Kaur R, Anand R, Shukla S, Mandal P (2020) Clinical profile and microbiologic spectrum of febrile neutropenic episodes in children with severe aplastic anemia. J Pediatr Hematol Oncol 42(3):193\u2013197","journal-title":"J Pediatr Hematol Oncol"},{"issue":"7","key":"6874_CR10","doi-asserted-by":"publisher","first-page":"3799","DOI":"10.1128\/AAC.02561-14","volume":"58","author":"RG Rosa","year":"2014","unstructured":"Rosa RG, Goldani LZ (2014) Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother 58(7):3799\u20133803","journal-title":"Antimicrob Agents Chemother"},{"key":"6874_CR11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1053\/j.seminhematol.2009.03.008","volume":"46","author":"JM Valdez","year":"2009","unstructured":"Valdez JM, Scheinberg P, Young NS, Walsh TJ (2009) Infections in patients with aplastic anemia. Semin Hematol 46:269\u2013276","journal-title":"Semin Hematol"},{"key":"6874_CR12","first-page":"102","volume-title":"Lanzkowsky ped. Manual of pediatric hematology and oncology","author":"JM Lipton","year":"2016","unstructured":"Lipton JM (2016) Bone marrow failure. Lanzkowsky ped. Manual of pediatric hematology and oncology, 6th ed. Elsevier, San Diego, CA, pp 102\u201334","edition":"6th ed"},{"key":"6874_CR13","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1093\/cid\/cir073","volume":"52","author":"AG Freifeld","year":"2011","unstructured":"Freifeld AG, Bow EJ, Sepkowitz KA et al (2011) Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 52:e56\u2013e93","journal-title":"Clin Infect Dis"},{"key":"6874_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1086\/599376","volume":"49","author":"LA Mermel","year":"2009","unstructured":"Mermel LA, Allon M, Bouza E et al (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49:1\u201345. https:\/\/doi.org\/10.1086\/599376","journal-title":"Clin Infect Dis"},{"key":"6874_CR15","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","volume":"71","author":"JP Donnelly","year":"2020","unstructured":"Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG (2020) 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. Clin Infect Dis 71:1367\u20131376","journal-title":"Clin Infect Dis"},{"key":"6874_CR16","unstructured":"Vlachos A, Lipton JM (2011) Bone marrow failure. In: Lanzkowsky P, Lipton JM, Fish JD, editors. Manual of Pediatric Hematology and Oncology. 7th ed. London: Academic Press; p.100"},{"key":"6874_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/s12878-018-0129-9","volume":"18","author":"R Lertpongpiroon","year":"2018","unstructured":"Lertpongpiroon R, Rattarittamrong E, Rattanathammethee T, Chai-Adisaksopha C, Tantiworawit A, Salee P, Norasetthada L (2018) Infections in patients with aplastic Anemia in Chiang Mai University. BMC Hematol 18:35. https:\/\/doi.org\/10.1186\/s12878-018-0129-9","journal-title":"BMC Hematol"},{"issue":"3","key":"6874_CR18","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1007\/s12288-022-01597-z","volume":"39","author":"SA Lionel","year":"2023","unstructured":"Lionel SA, Selvarajan S, Korula A, Kulkarni U, Devasia A, Abubacker FN, Abraham A, Mathews V, Lakshmi KM, George B (2023) Profile and predictors of infection following anti-thymocyte Globulin or anti-lymphocyte Globulin with cyclosporine in aplastic anemia. Indian J Hematol Blood Transfus 39(3):419\u2013428. https:\/\/doi.org\/10.1007\/s12288-022-01597-z","journal-title":"Indian J Hematol Blood Transfus"},{"issue":"1","key":"6874_CR19","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.htct.2019.05.006","volume":"42","author":"P Perez","year":"2020","unstructured":"Perez P, Pati\u00f1o J, Estacio M, Pino J, Manzi E, Medina D (2020) Bacteremia in pediatric patients with hematopoietic stem cell transplantation. Hematol Transfus Cell Ther 42(1):5\u201311. https:\/\/doi.org\/10.1016\/j.htct.2019.05.006","journal-title":"Hematol Transfus Cell Ther"},{"issue":"45","key":"6874_CR20","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001931","volume":"94","author":"L Wang","year":"2015","unstructured":"Wang L, Wang Y, Fan X, Tang W, Hu J (2015) Prevalence of resistant Gram-negative bacilli in bloodstream infection in febrile neutropenia patients undergoing hematopoietic stem cell transplantation: a single center retrospective cohort study. Medicine (Baltimore) 94(45):e1931","journal-title":"Medicine (Baltimore)"},{"issue":"1","key":"6874_CR21","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s00277-018-3487-2","volume":"98","author":"S Shah","year":"2019","unstructured":"Shah S, Jain P, Shah K, Patel K, Parikh S, Patel A, Panchal H, Anand A (2019) Immunosuppressive therapy for aplastic anemia: a single-center experience from Western India. Ann Hematol 98(1):41\u201346","journal-title":"Ann Hematol"},{"key":"6874_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2024.102860","volume":"108","author":"A Guarina","year":"2024","unstructured":"Guarina A, Farruggia P, Mariani E, Saracco P, Barone A, Onofrillo D, Cesaro S, Angarano R, Barberi W, Bonanomi S, Corti P, Crescenzi B, Dell\u2019Orso G, De Matteo A, Giagnuolo G, Iori AP, Ladogana S, Lucarelli A, Lupia M, Martire B, Mastrodicasa E, Massaccesi E, Arcuri L, Giarratana MC, Menna G, Miano M, Notarangelo LD, Palazzi G, Palmisani E, Pestarino S, Pierri F, Pillon M, Ramenghi U, Russo G, Saettini F, Timeus F, Verzegnassi F, Zecca M, Fioredda F, Dufour C (2024) Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP). Blood Cells Mol Dis 108:102860","journal-title":"Blood Cells Mol Dis"},{"issue":"5","key":"6874_CR23","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1056\/NEJMoa1103975","volume":"365","author":"P Scheinberg","year":"2011","unstructured":"Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, Young NS (2011) Horse versus rabbit antithymocyte Globulin in acquired aplastic anemia. N Engl J Med 365(5):430\u2013438","journal-title":"N Engl J Med"},{"issue":"2","key":"6874_CR24","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s12288-019-01158-x","volume":"37","author":"B Dutta","year":"2021","unstructured":"Dutta B, Dolai TK, Mandal PK, Baul S, De R, Senthil K et al (2021) Response to immunosuppressive therapy in acquired aplastic anaemia: experience of a tertiary care centre from Eastern India. Indian J Hematol Blood Transfus 37(2):197\u2013203","journal-title":"Indian J Hematol Blood Transfus"},{"issue":"1","key":"6874_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3324\/haematol.10075","volume":"92","author":"A Locasciulli","year":"2007","unstructured":"Locasciulli A, Oneto R, Bacigalupo A, Soci\u00e9 G, Korthof E, Bekassy A et al (2007) Outcome of patients with acquired aplastic anemia given frst line bone marrow transplantation or immunosuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation (EBMT). Haematologica 92(1):11\u201318","journal-title":"Haematologica"},{"issue":"6","key":"6874_CR26","doi-asserted-by":"publisher","first-page":"e2413955","DOI":"10.1001\/jamanetworkopen.2024.13955","volume":"7","author":"RD Lane","year":"2024","unstructured":"Lane RD, Richardson T, Scott HF, Paul RM, Balamuth F, Eisenberg MA, Riggs R, Huskins WC, Horvat CM, Keeney GE, Hueschen LA, Lockwood JM, Gunnala V, McKee BP, Patankar N, Pinto VL, Sebring AM, Sharron MP, Treseler J, Wilkes JJ, Workman JK (2024) Delays to antibiotics in the emergency department and risk of mortality in children with sepsis. JAMA Netw Open 7(6):e2413955","journal-title":"JAMA Netw Open"},{"key":"6874_CR27","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1186\/1471-2334-14-286","volume":"14","author":"RG Rosa","year":"2014","unstructured":"Rosa RG, Goldani LZ, dos Santos RP (2014) Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropenia: a prospective cohort study. BMC Infect Dis 14:286","journal-title":"BMC Infect Dis"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-06874-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06874-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06874-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:20:33Z","timestamp":1786785633000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-06874-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["6874"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-06874-9","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"14 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Informed consent was obtained from the legal guardians of all individual participants included in the study. No personally identifiable information was used.","order":1,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"338"}}