Long-term antifungal prophylaxis in high-risk hematopoietic stem cell transplant recipients

The risks for invasive fungal infections, particularly mould infections such as invasive aspergillosis, among hematopoietic stem cell transplant (HSCT) recipients are linked to the duration and severity of myelosuppression and immunosuppression. Strategies to prevent invasive fungal infections have focused primarily on the use of orally administered azole antifungal agents during the neutropenic period rather than on the more prolonged post-engraftment period. The major limitations of these studies included the heterogeneity among the subjects studied for fungal infection risk factors, the agents administered, the dosing, and duration of prophylaxis. More recent studies have attempted to examine the efficacy of antifungal prophylaxis strategies among allogeneic HSCT recipients to day 100 and beyond. It is clear that a variety of products have efficacy in preventing invasive candidiasis, including imidazole and triazole antifungals, low-dose amphotericin B, and the echinocandin, micafungin; however, only the extended spectrum azole, itraconazole, has been shown to impact the incidence of proven invasive aspergillosis. Other extended spectrum azole antifungal agents, voriconazole and posaconazole, are being studied as long-term prophylaxis in high-risk HSCT recipients. While clinical trials have suggested that a duration of prophylaxis against moulds of six months or more may be required, it remains unclear if this is required in all cases. The prophylactic efficacy over time may be linked to the degree of immunosuppression as measured by markers such as the numbers of circulating CD4 T lymphocytes. Concerns about selection for resistant moulds among long-term recipients of these drugs are emerging. The cumulative experience to date suggests that long-term antifungal chemoprophylaxis is feasible and effective when applied in defined circumstances. The concerns about treatment-related toxicities, resistance, and costs are valid.