Clinical and microbiological insights into invasive fusariosis following allogeneic hematopoietic stem cell transplantation: A 15-year single-center analysis

Abstract

Abstract Introduction: Invasive fusariosis (IF) is a rare but life-threatening fungal infection that mainly affects immunocompromised patients. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are particularly vulnerable due to profound immunosuppression, including prolonged neutropenia. Despite advances in antifungal prophylaxis and treatment, IF in this population remains associated with unacceptably high mortality. However, no studies have comprehensively evaluated IF in this setting focusing on patient characteristics, Fusarium species distribution, antifungal susceptibility, and clinical outcomes. To address this gap, we conducted a single-center study to assess the incidence, microbiological features, antifungal susceptibility, and survival outcomes of IF in allogeneic HSCT recipients. Methods: All patients who underwent allogeneic HSCT for hematologic malignancies between 2010 and 2024 at our center were retrospectively reviewed, and those diagnosed with proven IF were included. The definition of proven IF was based on the revised definitions of the European Organization for Research and Treatment of Cancer Invasive Fungal Infections Cooperative Group Infectious Diseases Mycoses Study Group. Identification was performed through sequencing of the internal transcribed spacer and D1/D2 regions of the ribosomal DNA, as well as the tef1 and rpb2 genes of the isolated Fusarium species and drug susceptibility tests were performed on the basis of the Clinical and Laboratory Standards Institute M38-A2 prior to June 2024, and M38-Third Edition thereafter. Baseline characteristics between patients with and without IF were compared using appropriate parametric and non-parametric tests. Overall survival (OS), and day 28, 84, and 1-year mortality were estimated using the Kaplan–Meier method, and univariate comparisons of clinical factors—including age, sex, performance status, conditioning intensity, prior HSCT, neutrophil recovery, monotherapy vs combination therapy with liposomal amphotericin B (L-AMB) and voriconazole (VRCZ), and steroid use—were conducted using the log-rank test. Results: Seventeen patients with proven IF and 2,342 without IF were analyzed. The incidence of IF among allogeneic HSCT recipients was 7.2 cases per 1,000 transplants. Most cases occurred in patients transplanted in non-complete remission (94.1% vs. 75.8% in non-IF, P = 0.091). Prior allogeneic HSCT was significantly more common in the IF group (58.8% vs. 19.8%, P = 0.002), while age, sex, underlying disease, and donor source showed no significant differences. Among IF cases, donor sources were cord blood (n=14), matched related donor (n=1), and haploidentical donor (n=2). The median time from transplantation to IF onset was 10 days (range, 1–998), with a median neutrophil count of 0/μL (range, 0–7,500) at diagnosis; 11 patients (64.7%) had not achieved engraftment. All patients received antifungal prophylaxis: micafungin (n = 10), posaconazole (n = 4), or VRCZ (n = 3). Fusarium species distribution was: F. solani species complex (n = 11), F. dimerum species complex (n = 4), and F. fujikuroi species complex (n = 2). All isolates had high MECs for micafungin at 24 h (>16 μg/mL). The 48 h MIC for amphotericin B had a median of 4 μg/mL (range, 1–>16), and for VRCZ was >8 μg/mL (range, 2–>8). Treatment included L-AMB monotherapy in 9 patients (52.9%) and L-AMB plus VRCZ in 6 patients (35.3%). The median OS was 13 days (95% CI, 7–31). Mortality was 70.6% at Day 28 (12/17), 82.4% at Day 84 (14/17), and 94.1% at 1 year (16/17). Causes of death included IF (n = 10, 58.8%), sepsis due to non-IF infections (n = 4, 23.5%), disease relapse (n = 1), and intracranial hemorrhage (n = 1). In univariate analysis, combination therapy (P = 0.013) and neutrophil recovery (P = 0.008) were associated with improved Day 84 survival. No clear trends were noted in species distribution or antifungal susceptibility between survivors and non-survivors. Discussion: This study is the first comprehensive analysis of IF in allogeneic HSCT recipients, linking clinical and microbiological features to outcomes. Patients with IF were more likely to have uncontrolled underlying disease, and profound neutropenia was frequent at diagnosis. The prognosis was extremely poor, and although no clear trends were observed in Fusarium species or antifungal susceptibility, neutrophil recovery and combination therapy with L-AMB and VRCZ may be crucial for improving outcomes.