Predictors of Febrile Neutropenia and Role of Levofloxacin Prophylaxis in Acute Myeloid Leukemia And High-Risk Myelodysplastic Syndrome Patients Treated With Hypomethylating Agents

Abstract

Introduction: Prevention of febrile neutropenia in Acute Myeloid Leukemia (AML) and High-Risk Myelodisplastic Syndrome (HR-MDS) patients undergoing treatment with hypomethylating agents (HMAs) remains controversial and there are no clinical guidelines for infection prophylaxis in these clinical settings. Methods: We retrospectively analyzed the impact of quinoline prophylaxis (QP) with levofloxacin on incidence of febrile neutropenia (FN) in 141 consecutive AML (n=98) and HR-MDS (n=43) patients receiving a total of 1550 courses of HMAs between April 2008 and December 2019 at our Institute. Results: One-hundred-thirty-seven episodes of FN occurred, 82 of which required hospitalization. COPD (p = 0.01, HR =1.9), prior hospital admission (p G1 during treatment (p=0.01, HR=1.8) emerged as significant factors affecting development of FN. Patients with more than one of the above-mentioned risk factors had a 6-fold increased cumulative risk to develop FN after 6 cycles of HMAs (24% vs 4%, p=0.01). In the whole population, levofloxacin prophylaxis did not significantly reduce the risk of FN in any risk subgroups. However, in AML population, levofloxacin prophylaxis was able to prevent febrile neutropenia episodes in patients with neutrophils count <1000/mcl at Day1 of the cycle (p<0.01). Conclusions: Hospital bacterial colonization, mucosal interruption and neutropenia were found to be the main risk factors to the development of FN in patients with AML and HR MDS treated with HMAs. Levofloxacin prophylaxis was not able to overcome these risk factors. However, in AML patients with neutropenia at the start of HMA cycle, levofloxacin significantly reduced the incidence of FN episodes. Further studies are needed to identify strategies to lower FN in this patient population.