Voriconazole used as antifungal prophilaxis decreases invasive fungal disease in patients undergoing allogenic stem cell transplantation in our institution (Allo-SCT).

MARIA JOSE LLAMAS POYATO* 1, CAROLINA CHIC ACEVEDO1, ESTEFANIA GARCIA TORRES1, JOSEFINA SERRANO LOPEZ1, JOSE RAMON MOLINA HURTADO1, CARMEN MARTIN CALVO1, FRANCISCO MARTINEZ GUIBELARDE1, RAFAEL ROJAS CONTRERAS1

Author address: 

1HEMATOLOGY, REINA SOFIA UNIVERSITY HOSPITAL, CORDOBA, Spain

Abstract: 

Introduction: Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing Allo-SCT. Some new triazole-drugs with anti-filamentous activity (as Voriconazole) have being used during the last years as antifungal prophylaxis for high-risk patients.The aim of our study was to compare the incidence of IFD in patients undergoing Allo-SCT in our institution using Fluconazole vs Voriconazole as prophylactic treatment.
Materials (or patients) and methods: We analyse retrospectively 196 allo-SCT consecutive patients (paediatrics and adults) submitted to this procedure in our center from March 2001 to April 2008. A total of 98 patients received antifungal prophylaxis with Fluconazole and 98 with Voriconazole. All patients received antifungal prophylaxis with oral Voriconazole 200 mg/12 hours (5mg/kg/12h in children) or Fluconazole 200 mg/12 hours (5mg/kg/day in children) from day 0 to day +75. Antifungal prophylaxis was prolonged in patients requiring treatment with high doses of corticosteroids (> 2mg/kg/day) and/or with 2 immunosuppressive drugs. The temporary suspension was applied in those patients with toxicity,without reaching criteria for withdrawal,being able to continue the study drug if the suspected toxicity resolved in 7 days. AGA detection was done twice weekly from year 2004. It was considered positive when the index OD was ≥ 0.5 in 2 consecutive measurements or ≥ 0.8 on a single determination. When IFD was suspected a new determination of AGA and a high resolution CT were done as well as a bronchoalveolar lavage. IFDs were according to the revised criteria of the EORTC/MSG 2008. Drug toxicity was evaluated according to CTCAEv4.1 criteria.
Results: We found differences between the 2 groups in terms of: type of graft (bone marrow was more frecuently in fluconazole group), regimen and type of conditioning (reduced-intensity conditioning was more common in voriconazole group) and presence of cGVHD (more frecuenty in voriconazol group). The incidence of IFD was 16.3% in the Fluconazole group (n=16) vs 7.1% (n=7) in Voriconazole group (P=0.046). The median of FFS was 24.5 days and 106 days (P=0.003). According to the EORTC/MSG criteria,taking into account only patients who developed IFD, the percentage of possible IFD in the first group was 50% vs 14.8% in the second group; Probable: 37.5% vs. 71.4%; Proven: 12.5% vs. 14.28%. We found significant statistical differences at 360 days post SCT (83.7% vs 92.9%;P=0.034). Deaths caused by IFD were 10.1% in Fluconazole (n=10) and 3.1% in Voriconazole (n=3) (P=0.027). The median follow-up was 34 months. There was no significant difference in overall survival: 52.1% vs 52.6% (P=0.95). There were no differences in causes of death (P=0.326). Eleven patients (11.22%) presented adverse effects (AE)in the first group vs 18 patients (18.36%) in the second one (P = 0.065). The most frequent AE for both groups was hepatic toxicity. There were not significant differences in the suspension (temporary and permanent) of the drug between the two groups.
Conclusion: This study confirms that the use of Voriconazole as antifungal prophylactic treatment in patients undergoing allo-SCT decreases the incidence of IFD and increases FFS versus Fluconazole. In spite of a greater toxicity in Voriconazole group,this toxicity was non severe and rapidly recovered with the withdrawal of the drug.

2015

abstract No: 

P036

Full conference title: 

European Society for Blood and Marrow Transplantation
    • EBMT 41st (2015)