Incidence of Febrile Neutropenia in Newly Diagnosed Acute Myeloid Leukaemia Patients during Intensive Induction Chemotherapy: A Systematic Review and Meta-Analysis

Background Febrile neutropenia (FN) is a life-threatening complication of intensive induction chemotherapy for acute myeloid leukaemia (AML) [1]. It is the leading cause of treatment-related mortality and adversely affects remission as well as overall survival. The reported incidence of febrile neutropenia is high and heterogeneous. This systematic review and meta-analysis aim to estimate the pooled incidence of FN during AML induction and to characterize associated infections to enhance optimal management of these high-risk patients. Methods The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42024628474) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Eligible studies included adults (≥ 18 years) with newly diagnosed AML patients undergoing intensive induction (7 + 3-like anthracycline–cytarabine regimens). We searched PubMed, Embase, Scopus, and Web of Science for the last 10 years from 1st of December 2024. Febrile neutropenia incidence proportions were pooled using a Der Simonian–Laird random-effects model after logit transformation. Heterogeneity was assessed with the I² (I-squared) statistic, and leave-one-out sensitivity analyses were conducted to evaluate result robustness. An artificial intelligence language model (ChatGPT, OpenAI) was used solely to assist with language editing and clarification. Results Three studies were included in the final analysis, all conducted in Asian countries classified as high- or upper-middle-income settings. The pooled incidence of febrile neutropenia during induction chemotherapy was 88% (95% CI, 76%–95%). Considerable heterogeneity was observed (I² = 85%), due to differences in definitions of febrile neutropenia, chemotherapy protocols, and supportive care practices. One study with a narrow febrile neutropenia definition was included only in sensitivity analyses to maintain methodological consistency. However, the pooled estimates remained stable (ranging from 85% to 93%) upon sequential exclusion of individual studies. Gram-positive cocci were the predominant pathogens, and Aspergillus species accounted for the majority of fungal infections. All included studies had moderate to high risk of bias, mainly due to inconsistent febrile neutropenia definitions and limited microbiological documentation. Conclusions Febrile neutropenia occurs at a very high frequency during AML induction, highlighting the importance of vigilant infection prophylaxis and prompt empirical therapy. Adoption of the standard febrile neutropenia definition and supportive care planning is recommended to improve treatment outcomes in AML induction.