The Effectiveness of Levofloxacin in Prevention of Febrile Episodes in Non-Hodgkin Lymphoma Patients Receiving Rituximab, Cyclophosphamide, Vincristine, Doxorubicin and Prednisolone (R-CHOP)

Background: Febrile neutropenia poses significant risks for morbidity and mortality in non-Hodgkin lymphoma (NHL) patients undergoing R-CHOP chemotherapy. Prophylactic antibacterial use after R-CHOP is controversial, especially when patients receive primary G-CSF prophylaxis, with no established standard recommendation. This study aims to evaluate the effectiveness of levofloxacin in preventing febrile episodes in NHL patients receiving R-CHOP and G-CSF prophylaxis. Method: A randomized, single-blind, placebo-controlled trial was conducted at King Chulalongkorn Memorial Hospital, enrolling non-Hodgkin lymphoma patients undergoing R-CHOP chemotherapy from January 1, 2023, to June 30, 2024. Patients were randomly assigned to receive either levofloxacin 500 mg once daily or a matching placebo for 7 days, beginning one day after chemotherapy. All patients received primary G-CSF prophylaxis. The primary outcome was the occurrence of febrile episodes within 120 days. Secondary outcomes included rates of septic shock, septic death, all-cause mortality, chemotherapy dose reduction, and the onset of the first febrile episode and composite outcome. Results: Eighty participants were randomly assigned to two groups, with 40 individuals in each group. Their mean age was 61 years. In the intention-to-treat analysis, febrile episodes occurred in 7.5% and 30% of participants in the levofloxacin and placebo groups, respectively (P = 0.010). Levofloxacin prophylaxis significantly reduced febrile neutropenia (2.5% vs. 20%, P = 0.013), chemotherapy dose reduction (0% vs. 12.5%, P = 0.021), and composite outcome (10% vs. 30%, P = 0.025). The hazard ratio for febrile-free survival with levofloxacin vs. placebo was 0.23 (95% CI 0.06 to 0.8; P = 0.012). No significant differences in infection-related mortality or all-cause mortality were observed between the two groups. Furthermore, no serious adverse effects were documented in either group. Conclusions: The use of levofloxacin prophylaxis is an effective and well-tolerated strategy in reducing the incidence of febrile episodes, febrile neutropenia, and the need for chemotherapy dose reduction among NHL patients undergoing R-CHOP chemotherapy despite primary G-CSF prophylaxis. Long-term antibiotic resistance monitoring is needed.