Antifungal Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

Abstract

TO THE EDITOR: In the article by Michallet and Ito, the authors provided an excellent comprehensive review of the literature; however, the recommendations for allogeneic hematopoietic cell transplantation prophylaxis outlined in Table 5, “Author Recommendations for Prophylaxis,” are surprising. Three agents are recommended for primary prophylaxis during overlapping time periods. The literature shows that neither micafungin nor voriconazole yield a survival advantage over fluconazole, the standard of care. The authors recommended fluconazole for primary neutropenia through day 75 and voriconazole for neutropenia through day 100. A head-tohead to study between voriconazole and fluconazole reported a decrease in aspergillosis in the voriconazole arm; however, the rates of invasive fungal infection, fungal-free survival, and overall mortality were similar between both groups. The study drugs were administered for 100 days in both arms, which indicates that fluconazole had similar efficacy through day 100. It seems premature to recommend micafungin as primary prophylaxis for “neutropenia through engraftment,” since the standard of care and the authors themselves recommend prophylaxis for 75 to 100 days post-transplant. Although the authors mentioned the possibility of sequencing prophylaxis (micafungin followed by either fluconazole or voriconazole), there are no data to support this approach. In addition, in the trial comparing micafungin to fluconazole, there was not a survival benefit for micafungin as noted by Michallat and Ito, and the other end points were not comparable to the studies reviewed. From the evidence presented, there does not appear to be a strong rationale for the use of voriconazole or micafungin when compared with fluconazole. Furthermore, it should be noted that fluconazole is generic and costs significantly less than voriconazole or micafungin. Based on the evidence and cost considerations, fluconazole seems to be the optimal antifungal agent for prophylaxis in allogeneic hematopoietic stem-cell transplant recipients. Our familiarity with this literature is based on our current work conducting a cost-effectiveness analysis of prophylactic antifungal therapy in patients undergoing allogeneic hematopoietic stem-cell transplant. We presented this work at the annual meeting of the Society for Medical Decision Making, October 18-21, 2009, in Hollywood, CA.