Vol.74 No.1 January 2026
Clinical predictors of the need for second-line treatment for febrile neutropenia among patients with hematological malignancies
1)Department of Pharmacy, Tenshi Hospital, N12-E3-1-1 Higashi-ku, Sapporo, Hokkaido, Japan
2)Department of Hematology, Tenshi Hospital
3)Department of Surgery, Tenshi Hospital
Abstract
Febrile neutropenia (FN) is a frequent complication of chemotherapy in patients with hematological malignancies and is associated with an elevated risk of severe infections and impaired treatment outcomes. Most Japanese guidelines recommend monotherapy with an anti-pseudomonal β-lactam antibiotic as the first-line treatment, the optimal strategy for second-line treatment remains unclear. This study was aimed at investigating the clinical characteristics and other factors associated with the need for second-line treatment for FN in patients with hematological malignancies receiving cefepime (CFPM) monotherapy as the initial treatment. We retrospectively analyzed the data of 69 patients with hematological malignancies who were admitted to Tenshi Hospital between January 2015 and December 2022. All the patients developed FN during chemotherapy and received CFPM monotherapy as first-line treatment. Patients who successfully completed the initial CFPM monotherapy were defined as the primary treatment group (pt group, n=30), while those who required additional antimicrobial agents were classified as the second-line treatment group (st group, n=39). The patient characteristics and treatment outcomes were compared between the two treatment groups. The treatment success rate was 86.7% (26/30) in the pt group and 43.6% (17/39) in the st group. The st group showed significantly higher baseline serum C-reactive protein (CRP) levels as compared with the pt group (median: 7.6 mg/dL vs. 2.3 mg/dL, p=0.0026). Elevated serum CRP, with a CRP cutoff value of 6.43 mg/dL determined by receiver operating characteristic curve analysis, was identified as a predictor of the need for second-line treatment for FN. Logistic regression analysis identified an elevated baseline serum CRP level and history of FN within the previous three months as significant predictors of the need for secondary treatment for FN (p=0.0059, p=0.0047). The results of this study suggest that a baseline serum CRP level of ≥6.43 mg/dL and a history of FN within the previous three months are potential risk factors for a reduced efficacy of the initial CFPM monotherapy for FN in patients with hematological malignancies. Therefore, careful monitoring of the clinical course is essential, particularly for patients with the two aforementioned risk factors. Where indicated, clinicians could consider broadening the antimicrobial spectrum of the initial treatment beyond that of CFPM and/or initiating concomitant therapy with an anti-methicillin-resistant Staphylococcus aureus agent and/or antifungal agent.
Key word
febrile neutropenia, hematological malignancy, second-line treatment, risk factor
Received
March 28, 2025
Accepted
October 6, 2025
Jpn. J. Chemother. 74 (1): 25-33, 2026
