Prolonged Fluconazole Prophylaxis Is Not Required In Patients With Acute Leukemias Or Myelodysplastic/Myeloproliferative Disorders After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT): A Pair-Matched Analysis
Authors: Brissot Eolia , Cahu Xavier , Guillaume Thierry , Delaunay Jacques , Ayari Sameh , Precupanu Cristina , Peterlin Pierre , Harousseau Jean-Luc , Milpied Noel , Moreau Philippe , Mohty Mohamad , Chevallier Patrice 
Published: October 2019

Introduction
Invasive fungal infections (IFI) due to Candida and Aspergillus species remain a major complication of allo-SCT. In the myeloablative setting, previous studies have demonstrated that fluconazole, administered for 75 days after transplant (400 mg/d), in a prophylaxis setting, can allow for a decreased risk of gut GVHD and disseminated candida infections or candidiasis-related death, resulting in an overall survival benefit (Marr et al., Blood 2000). However, to our knowledge, there is currently no study, addressing the potential benefit of fluconazole prophylaxis in the setting of reduced-intensity conditioning (RIC) allo-SCT.

Methods
This retrospective study included 105 patients with acute leukemia (AML, n=55, ALL, n=11) or myelodysplastic/myeloproliferative disorders (MDS, n=24; myeloproliferative disorder n=15) who received an allo-SCT between January 2000 and December 2011. In this series, patients received one (n=105) or two (n=4) RIC allo-SCT and PBSC as stem cell source for all. Among these 109 procedures, we compared those cases receiving (n=53) or not (n=56) fluconazole prophylaxis after transplant. The post-transplant fluconazole prescription or not was at the discretion of the attending physician and was homogeneous for each physician. There were not significant differences between both groups in terms of gender, median age (fluco: 55 vs 57 years), median follow-up (fluco: 42 months (range: 19-76) vs 37 months (range: 11-124)), median year of transplant (fluco: 2008 (range: 2003-2011) vs 2009 (range: 2000-2011)), type of disease and disease status at time of transplant or type of donor.

Results
The median time of fluconazole administration (400mg/day) after transplant was 88 days (range: 7-324). Fluconazole was stopped only in 2 patients because of (reversible) liver cytolysis. Before day +100, only 2 Aspergillus infections were documented in the fluconazole group vs 4 in the non-fluconazole group (P=NS). No Candida infections (septicemia or cutaneous candidiasis) developed in the fluconazole group compared to 2 in the non-fluconazole group (P=NS). After day +100, Aspergillus infections were documented in 5 patients in the fluconazole group versus 3 in the non-fluconazole group (P=NS). The number of patients receiving pre-emptive or curative antifungal treatment (voriconazole, caspofungin or ambisome) after transplant was higher in the non-fluconazole group (52% of cases vs 34%, P=0.09).
3-year OS, DFS and NRM were similar between both groups (fluco: 42% vs 51%, P=0.42, fluco: 38% vs 46%, P=0.62, and fluco: 28% vs 23%, p=0.67). Also, there were no significant differences in term of cumulative incidences of acute grade II-IV GVHD (fluco: 27% vs 36%, P=0.29), acute grade III-IV GVHD (fluco: 21% vs 18%, P=0.42) or chronic GVHD (fluco: 47% vs 33%, P=0.67).

Conclusion
This is the first series reporting the comparison of the use or not of fluconazole as prophylaxis after RIC allo-SCT. Our results showed that the use of fluconazole has no impact in term of fungal infections or overall outcomes after RIC allo-SCT, suggesting that fluconazole is not required after RIC allo-SCT. Large prospective studies are warranted to further confirm this important therapeutic issue.

Disclosures:
Moreau: CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau. Mohty:Novartis: Honoraria, Research Support Other.