Randomized trial of prophylaxis with intravenous micafungin during haematopoietic stem cell transplantation

Silvia Park*, Su-Hee Cho, Chul Won Jung Jung, Jun Ho Jang, Kihyun Kim, Su Jin Lee, Won Jin Chang, Jung Yong Hong, Moon Ki Choi, Ji Yun Lee, Sung Hee Lim

Author address: 

Seoul, KR


Introduction: Invasive fungal infections cause significant morbidity and mortality in HSCT recipients. Although fluconazole has been widely used for antifungal prophylaxis in these patients, it is not effective against invasive aspergillosis. Micafungin provides antifungal activity against Candida and Aspergillus species, and previous studies have demonstrated its efficacy when used as a prophylactic agent for fungal infection in neutropenic patients. Here, we evaluated and compared the incidence rate of proven or probable invasive fungal infections (IFIs) with antifungal prophylaxis using micafungin or fluconazole. 
Methods: This is a prospective, single center, phase II, ongoing study involving adult patients who receive allogeneic or autologous HSCT. Patients were randomly assigned to micafungin (50mg/day i.v) or fluconazole arms (400mg/day p.o.) in the ratio of 2:1. The treatment was initiated within 24 hour of stem cell infusion, and lasted for up to 21 days of post-transplantation. 
Results: Between March 2010 and August 2012, a total of 74 patients were enrolled (micafungin, n=54; fluconazole, n=20). The main underlying disease for allogeneic transplantation (n=64) were acute myeloid leukemia (39%), acute lymphoid leukemia (27%) and myelodysplastic syndrome (11%); and multiple myeloma was the most common reason (60.0%) for autologous transplantation (n=10). Baseline characteristics were compared, and there was no significant difference in gender, transplantation type (allo vs auto), donor (sibling vs unrelated) and conditioning intensity (myeloablative vs reduced intensity) between two treatment arms. During study period, proven or probable IFIs were identified in 7 of 54 for micafungin arm (13%), and 3 of 20 for fluconazole arm (15%) (p=1.0). Overall mortality at 100 days after transplant was 14.9% (11/74), and patients who experienced proven or probable IFIs showed significantly higher mortality (6/10, 60%) than patients who did not (5/64, 7.8%) (p<0.001). Among treatment arms, 100-day mortality following HSCT was higher in fluconazole arm (4/20, 20%) compared to micafungin arm (7/54, 13%), although there was no statistical significance (p=0.474). 
Conclusion: In this preliminary result, the incidence of proven or probable invasive fungal infections (IFIs) in HSCT recipients with micafungin prophylaxis was comparable to that of fluconazole prophylaxis.


Full conference title: 

Annual Meeting of European Society for Blood and Marrow Transplantation
    • EBMT 39th (2013)