Low-dose fluconazole as a useful and safe prophylactic option in patients receiving allogeneic hematopoietic stem cell transplantation

Abstract

Background: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day).

Methods: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant.

Results: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group.

Conclusion: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation.

Keywords: allogeneic hematopoietic stem cell transplantation; fluconazole; fungal infection; fungal prophylaxis.

FIGURE 1

Flowchart of antifungal prophylaxis in the 107 patients who underwent allogeneic HSCT. FLCZ, fluconazole; HSCT, hematopoietic stem cell transplantation; ITCZ, itraconazole; MCFG, micafungin; VRCZ, voriconazole; ^†Fluconazole (FLCZ): 100 mg/day ^‡Six patients who underwent their second HSCT within 100 days were considered one transplantation case.

FIGURE 2

(A) Cumulative incidence of antifungal prophylaxis failure with FLCZ prophylaxis. (B) Overall survival following the first allogeneic HSCT. (C) Overall survival in the FLCZ prophylaxis and non‐FLCZ prophylaxis groups. (D) Overall survival in the success and failure groups of FLCZ prophylaxis. FLCZ, fluconazole; HSCT, hematopoietic stem cell transplantation; allo‐HSCT, allogeneic HSCT.