Emerging treatments
Haematopoietic growth factors in invasive aspergillosis (IA)
Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) produce a modest reduction in the duration of neutropenia. GM-CSF enhances the phagocytic activity of polymorphonuclear leukocytes and may have a role in older patients with acute myelogenous leukaemia and IA.[121] Rapid return of neutrophils may produce an inflammatory response. GM-CSF has been used alone or in combination with interferon gamma.[122] The combination may induce clinical response by the cytokine-mediated inflammatory process, and may be of use in patients with impaired cell-mediated immunity.
Granulocyte transfusions in invasive aspergillosis
Donor granulocyte transfusions have been anecdotally used with success in patients with profound neutropenia and severe fungal or bacterial infection. Prognostic factors include an adequate number of granulocytes infused, granulocyte compatibility between donor and recipient, and anticipated marrow recovery. The donors may need a stimulation regimen of corticosteroids and G-CSF.[123][124]
Interferon gamma in invasive aspergillosis
Interferon gamma augments innate and TH1-dependent immunity. It has been shown to increase the oxidative burst and fungicidal activity of polymorphonuclear leukocytes against A fumigatus hyphae in vitro. It also restores corticosteroid-induced suppressed activity of monocytes and leukocytes. Impaired production of interferon gamma has been reported in patients with chronic pulmonary aspergillosis.[125] The compound has been shown to be effective as prophylaxis in patients with chronic granulomatous disease and, in combination with other cytokines, has been successful in case reports of patients with IA.[35] In one retrospective, descriptive study, the addition of interferon gamma therapy for >12 months in patients with chronic pulmonary aspergillosis refractory to antifungals alone appeared to reduce the frequency of acute exacerbations and all-cause hospital admissions.[125] Several other cytokines (interleukin [IL]-12, IL-15, IL-18, and chemokines) are promising as adjunctive therapy against invasive fungal infections.[126]
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