Clinical Profile and Factors Associated with Mortality in Febrile Neutropenia among Children with Acute Lymphoblastic Leukemia: A Single-Center Study in Indonesia
Keywords:
febrile neutropenia, Acute lymphoblastic leukemia, clinical profile, Pediatric, mortality, IndonesiaAbstract
Background and aim: Febrile neutropenia (FN) is a life-threatening oncologic emergency in children with acute lymphoblastic leukemia (ALL), associated with substantial morbidity and mortality. This study aimed to describe the clinical profile of FN and identify factors associated with mortality in a resource-limited pediatric oncology setting.
Methods: An observational analytic study with a cross-sectional design was conducted using secondary data from electronic medical records of pediatric ALL patients with FN at Dr. Soetomo General Academic Hospital between January 2023 and July 2025. The unit of analysis was FN episodes. Demographic, clinical, microbiological, and outcome data were collected. Mortality-associated factors were analyzed using chi-square, Mann–Whitney U, and independent t-tests.
Results: A total of 135 patients with 206 FN episodes were analyzed (mean 1.52 episodes/patient). Most episodes occurred in children aged <5 years (51.9%) and males (58.3%). Febrile Neutropenia most commonly developed during induction chemotherapy (42.2%), with high-risk ALL protocol predominating (52.9%). Profound neutropenia was present in 36.9% of episodes. Culture positivity was found in 28.6% of episodes, with gram-negative bacteria predominating (54.9%), particularly Pseudomonas aeruginosa (15.69%). Overall episode mortality rate was 16.5% (34/206 episodes; 25.2% per patient). Factors significantly associated with mortality included high-risk protocol, profound neutropenia, positive cultures, prolonged hospitalization, prolonged fever, delayed ANC recovery, lower hemoglobin, lower platelet count, and lower ANC (p<0.05).
Conclusions: High-risk protocol, severe neutropenia, bacteremia, and unfavorable hematological parameters were associated with mortality, highlighting the need for tailored risk stratification and antimicrobial stewardship in pediatric oncology settings.
References
1. Martínez Campos L, Perez-Albert P, Ramis LF, et al. Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP), An Pediatr (Engl Ed). 2023. 98, pp. 446–59. doi: 10.1016/j.anpedi.2023.03.012
2. Cennamo F, Masetti R, Largo P, Argentiero A, Pession A, Esposito S. Update on Febrile Neutropenia in Pediatric Oncological Patients Undergoing Chemotherapy. Children (Basel). 2021;8(12):1086. Published 2021 Nov 25. doi:10.3390/children8121086
3. Boeriu E, Borda A, Vulcanescu DD, et al. Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients-A Systematic Review. Diagnostics (Basel). 2022;12(8):1800. Published 2022 Jul 25. doi:10.3390/diagnostics12081800
4. Escrihuela-Vidal F, Laporte J, Albasanz-Puig A, Gudiol C. Update on the management of febrile neutropenia in hematologic patients. Rev Esp Quimioter. 2019;32 Suppl 2(Suppl 2):55-8. PMID: 31475812
5. Permono B, Sutaryo, Ugrasena IDG, Windiastuti E dan Abdulsalam M, 2012. Buku Ajar Hematologi-Onkologi Anak. Jakarta: IDAI, p227-310.
6. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451-8. doi:10.1111/j.1365-2141.1976.tb03563.x
7. Hematology-Oncology Working Group, Indonesian Pediatric Society. Indonesian Childhood ALL Guideline. 2024. Indonesian Pediatric Society.
8. Antimicrobial Resistance Control Committee (KPRA), Dr. Soetomo General Academic Hospital. Antimicrobial Resistance Control Program (PPRA) guidelines. 2022 ed. Surabaya, Indonesia: Dr. Soetomo General Academic Hospital.
9. Erbaş İC, Çakıl Güzin A, Özdem Alataş Ş, et al. Etiology and Factors Affecting Severe Complications and Mortality of Febrile Neutropenia in Children with Acute Leukemia. Turk J Haematol. 2023;40(3):143-53. doi:10.4274/tjh.galenos.2023.2023.0185
10. Kara SS, Tezer H, Polat M, et al. Risk factors for bacteremia in children with febrile neutropenia. Turk J Med Sci. 2019;49(4):1198-205. Published 2019 Aug 8. doi:10.3906/sag-1901-90
11. Rondinelli PI, Ribeiro Kde C, de Camargo B. A proposed score for predicting severe infection complications in children with chemotherapy-induced febrile neutropenia. J Pediatr Hematol Oncol. 2006;28(10):665-70. doi:10.1097/01.mph.0000212996.94929.0b
12. Angelino G, Caruso R, D'Argenio P, et al. Etiology, clinical outcome, and laboratory features in children with neutropenia: analysis of 104 cases. Pediatr Allergy Immunol. 2014;25(3):283-9. doi:10.1111/pai.12177
13. Nguyen SN, Vu LT, Vu QV, Tran TT, Dinh VTT. Clinical Epidemiology Characteristics and Etiology of Febrile Neutropenia in Children: Analysis of 421 Cases. Hematol Rep. 2022;14(3):245-52. Published 2022 Aug 1. doi:10.3390/hematolrep14030034
14. Keng MK, Sekeres MA. Febrile neutropenia in hematologic malignancies. Curr Hematol Malig Rep. 2013;8(4):370-8. doi:10.1007/s11899-013-0171-4
15. Aldemir-Kocabaş B, Karbuz A, Pekpak E, et al. Effects of respiratory viruses on febrile neutropenia attacks in children. Turk J Pediatr. 2017;59(5):511-9. doi:10.24953/turkjped.2017.05.002
16. Islas-Muñoz B, Volkow-Fernández P, Silva-Zamora J, Ramírez-Ibarguen A, Cornejo-Juárez P. Mortality in patients with hematological malignancies, febrile neutropenia, and septic shock. J Infect Dev Ctries. 2024;18(2):235-42. Published 2024 Feb 29. doi:10.3855/jidc.17451
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