Invasive Fungal Disease in Allogeneic Hematopoietic Cell Transplantation: New Risk Factors and New Therapeutic Options in a Changing World

Invasive fungal diseases (IFD) have been recognized by WHO as of critical significance to human health requiring investment in surveillance, diagnostics, new treatments, and antifungal stewardship which should adopt a one health approach. IFD continue to complicate immunosuppressive therapies such as those for hematological malignancy and allogeneic hematopoietic cell transplantation (alloHCT) with a mortality of 30%-80%. However, new approaches to GVHD prophylaxis and treatment, longer survivorship, expanded access to transplantation, and haploidentical donors are changing the landscape of IFD post alloHCT. As well as expanding risk groups, the geographic reach of certain endemic infections is expanding due to climate change. Alongside these changes requiring clinicians to have heightened awareness of IFD even outside of traditional risk groups and geographic locations, new diagnostics and antifungal therapies are reaching the clinic. This is a timely development as rates of antifungal resistance to first line agents, such as azoles, are increasing and as more high-risk patients receive antifungal prophylaxis, more resistant mold infections are increasingly seen. This review will address the changes in the field of IFD in patients receiving alloHCT and the evolving knowledge on new antifungal treatment options.