ANTIFUNGAL EFFECTS OF YEAST-DERIVED RHU-GM-CSF IN PATIENTS RECEIVING HIGH-DOSE CHEMOTHERAPY GIVEN WITH OR WITHOUT AUTOLOGOUS STEM-CELL TRANSPLANTATION - A RETROSPECTIVE ANALYSIS

Systemic fungal infections (SFI) in patients receiving high-dose chemo therapy (HDC) are a frequent cause of morbidity and mortality, Preclin ical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulati ng factors (CSF), including GM-CSF, We conducted a retrospective descr iptive epidemiologic study to examine the characteristics of 145 conse cutive patients receiving HDC administered with or without autologous stem cell transplantation (ASCT) and who subsequently received either GM-CSF and G-CSF, G-CSF alone, GM-CSF +/- IL-3 or no CSF, The analysis of this patient population sought to define the incidence of SFI and its relationship to therapy with monocyte/macrophage-stimulating (MMS group) cytokines (GM-CSF and G-CSF; GM-CSF +/- IL-3) or to cytokines w hich do not result in monocyte/macrophage stimulation (NMMS group, G-C SF alone or no CSF). Risk factors for the development of SFI were bala nced between the MMS (n = 70) and NMMS (n = 75) groups. Two patients ( 2.9%) in the MMS and nine patients (12%) in the NMMS groups developed SFI, The risk ratio for developing SFI in the NMMS group compared to t he MMS group was 4.20 (P = 0.023). This relationship was confounded, h owever, by the diagnosis of hematologic tumor or solid tumor (RR = 3.1 5, P = 0.082). SFI was the primary cause or major contributing factor in five of the 10 total deaths in our study population. Four SFI-relat ed deaths occurred in the NMMS group and one SFI-related death occurre d in the MMS group. Our data suggest a protective role for GM-CSF, IL- 3 or other MMS cytokines in preventing SFI in patients receiving HDC, This should be further investigated as a potential complementary appro ach to conventional strategies in antifungal prophylaxis for patients receiving HDC.