Invasive fungal disease and the immunocompromised host including allogeneic hematopoietic cell transplant recipients: Improved understanding and new strategic approach with sargramostim

Abstract

In hosts with damaged or impaired immune systems such as those undergoing hematopoietic cell transplant (HCT) or intensive chemotherapy, breakthrough fungal infections can be fatal. Risk factors for breakthrough infections include severe neutropenia, use of corticosteroids, extended use of broad-spectrum antibiotics, and intensive care unit admission. An individual's cumulative state of immunosuppression directly contributes to the likelihood of experiencing increased infection risk. Incidence of invasive fungal infection (IFI) after HCT may be up to 5-8%. Early intervention may improve IFI outcomes, although many infections are resistant to standard therapies (voriconazole, caspofungin, micafungin, amphotericin B, posaconazole or itraconazole, as single agents or in combination). We review herein several contributing factors that may contribute to the net state of immunosuppression in recipients of HCT. We also review a new approach for IFI utilizing adjunctive therapy with sargramostim, a yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF).

Keywords: Colony-stimulating factor; Granulocyte-macrophage colony-stimulating factor; Hematopoietic cell transplantation; Invasive fungal infections; Mycoses; Sargramostim.