Characterization of Breakthrough Invasive Fungal Infections in Allogeneic Hematopoietic Cell Transplant Recipients Receiving Antifungal Prophylaxis

Document Type

Conference Proceeding

Publication Date

2-1-2026

Publication Title

Transplant Cell Ther

Keywords

antifungal agent, calcineurin inhibitor, cyclophosphamide, posaconazole, thymocyte antibody, voriconazole, adult, all cause mortality, antifungal activity, candidemia, central venous catheter, clinical feature, comorbidity, conference abstract, controlled study, drug combination, drug therapy, female, graft recipient, graft versus host reaction, high risk population, hospitalization, human, immunosuppressive treatment, invasive aspergillosis, major clinical study, male, matched unrelated donor, mortality, nonhuman, prevention, prophylaxis, retrospective study, risk factor, systemic mycosis, therapy

Abstract

Background: Despite routine antifungal prophylaxis (AF), breakthrough invasive fungal infections (IFI) still occur and are associated with poor outcomes in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Objectives: To characterize the clinical features, timing, and mortality from proven/probable IFI in allo-HCT recipients despite the use of antifungal prophylaxis and to recognize the key risk factors for post- transplant IF. Methods: A retrospective study of adults who underwent allo-HCT at Henry Ford Hospital between January 2021 and December 2024. Demographics, comorbidities, transplant-related data, antifungal exposure, and one-year post-HCT mortality are reported. Results: Among 102 allo-HCT recipients, the median age was 62 years [45.0, 69.0] and 61% were male. The most common indications for HCT were AML (39%), MDS (25%), and ALL (13%). Matched-unrelated donor was the most frequent HCT (60%). The most frequently used AF agents were voriconazole (50%) and posaconazole (36%), with a median duration of 83 days [70.0, 112.0]. GVHD prophylaxis agents included calcineurin inhibitors (92%), cyclophosphamide (21%), and Anti thymocyte globulins (16%). Seven (7%) allo-HCT recipients developed IFI, primarily candidemia (33%) and invasive aspergillosis (14%), with a median onset of 232 days [129.0, 265.0]. There were no significant differences in demographics, comorbidities, indications for HCT, or occurrence of GVHD when comparing IFI-HCT and no-IFI-HCT. However, IFI-HCT had higher prior Candida colonization (p = 0.014), pre-HCT use of voriconazole (p = 0.007), hospitalization within 30 days (p<0.001), central line in place (p<0.001), augmentation of immunosuppression due to relapsed malignancy or GVHD treatment (p = 0.002), and one-year all-cause mortality (p = 0.001) compared to no-IFI-HCT (Table 1, Figure 1). Conclusions: In this single center experience, 7% of allo-HCT recipients presented IFI despite AF and was associated with delayed onset and high mortality. Persistent or intensified immunosuppression potentially contributed to AF failure. Improved risk stratification and optimization of AF are needed to prevent breakthrough IFI and enhance survival in this high-risk population.

Volume

32

Issue

2

First Page

S552

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