Low-dose Liposomal Amphotericin B for Antifungal Prophylaxis in Prolonged Neutropenia Patients

Overview

This is a single-center, single-arm, observational clinical study evaluating the efficacy and safety of low-dose liposomal amphotericin B (50 mg/day, intravenous, once daily) for the prevention of invasive fungal infections in adult patients (aged 18-75 years) with hematological malignancies who develop prolonged neutropenia (absolute neutrophil count ≤0.5×10\^9/L, expected to last \>7 days) and are at high risk for invasive fungal disease. Participants are those who, per the treating physician's routine clinical decision, have been initiated on liposomal amphotericin B prophylaxis at 50 mg/day due to intolerance or toxicity to other antifungal agents. The primary outcome is the incidence of proven or probable invasive fungal disease. Secondary outcomes include incidence of pneumonia, persistent unexplained fever \>4 days, use of additional systemic antifungal therapy, and adverse events. A total of 30 participants will be enrolled. Data will be collected at baseline, during treatment, and within 7 days after treatment completion.

Invasive fungal disease (IFD) is a serious and life-threatening infection caused by pathogenic fungi such as Candida, Aspergillus, and Mucorales, commonly affecting immunocompromised patients with hematological malignancies and those undergoing hematopoietic stem cell transplantation. The incidence of IFD has increased significantly in recent years due to the use of intensive chemotherapy and immunosuppressive agents, which result in prolonged and profound neutropenia (absolute neutrophil count \<500/μL for ≥10 days). Effective antifungal prophylaxis is a critical strategy to reduce IFD-related morbidity and mortality in this high-risk population. Liposomal amphotericin B (L-AmB) is a broad-spectrum antifungal agent with potent activity against most pathogenic fungi, including azole-resistant strains such as certain Aspergillus and Mucorales species. It is recommended by multiple guidelines as a first-line treatment for candidemia, invasive aspergillosis, and mucormycosis. However, its optimal prophylactic dosing regimen remains unclear, with published studies using widely varying regimens ranging from fixed low-dose (e.g., 50 mg every other day) to intermittent high-dose schedules (e.g., 5 mg/kg twice weekly). This study proposes a prophylactic regimen of L-AmB at a fixed low dose of 50 mg/day administered intravenously once daily. This regimen is designed to provide sustained, continuous drug exposure throughout the high-risk neutropenic period, potentially offering superior protection compared to intermittent high-dose schedules while maintaining a favorable safety profile. This is a single-center, single-arm, observational clinical study. Participants will be adults aged 18-75 years with hematological malignancies who meet the NCCN 2025 V1 guideline criteria for high-risk IFD, including allogeneic hematopoietic stem cell transplantation, autologous hematopoietic cell transplantation with mucosal damage, acute leukemia, grade 3/4 graft-versus-host disease, myelodysplastic syndrome, lymphoma, multiple myeloma, chronic lymphocytic leukemia, treatment with purine analogues (fludarabine, clofarabine, nelarabine), chimeric antigen receptor (CAR) T-cell therapy, alemtuzumab therapy, with expected neutropenia \>7 days. Participants must have been initiated on L-AmB prophylaxis at 50 mg/day by the treating physician in routine clinical practice due to intolerance or toxicity to other antifungal agents. Key exclusion criteria include prior proven/probable IFD, active fungal infection at screening, significant hypokalemia, severe hepatic or renal impairment, NYHA Class III/IV heart failure, HIV/TPHA positivity, expected survival \<3 months, and pregnancy or lactation. A total of 30 participants will be enrolled. Data will be collected at three time points: baseline (Day -3 to 0), treatment period (from Day 1 until the end of L-AmB therapy), and follow-up (within 7 days after treatment completion). Assessments include complete blood counts, serum biochemistry, imaging (chest CT), microbiological tests (G/GM tests, blood cultures, bronchoalveolar lavage fluid cultures or NGS), and recording of neutropenia episodes, fever, pneumonia, and adverse events. IFD diagnosis will be classified according to the Sixth Revised Edition of the Diagnostic Criteria and Treatment Principles for Invasive Fungal Disease in Patients with Hematological Malignancies. The primary outcome is the incidence of proven or probable IFD. Secondary outcomes include: (1) incidence of pneumonia with no identified pathogen; (2) proportion of patients with persistent unexplained fever \>4 days; (3) proportion of patients requiring additional systemic antifungal therapy; (4) discontinuation rate due to adverse effects or intolerance; and (5) incidence of adverse events graded according to CTCAE Version 5.0. The study is expected to enroll patients from August 2025 to August 2026, with final data analysis and report writing completed by November 2026. This study is approved by the institutional ethics committee and will be conducted in accordance with the Declaration of Helsinki. Informed consent will be obtained from all participants or their legal representatives.