title: 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.
abstract: Systemic fungal infections (SFI) in patients receiving high-dose chemotherapy (HDC) are a frequent cause of morbidity and mortality. Preclinical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulating factors (CSF), including GM-CSF. We conducted a retrospective descriptive epidemiologic study to examine the characteristics of 145 consecutive 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 which do not result in monocyte/macrophage stimulation (NMMS group, G-CSF alone or no CSF). Risk factors for the development of SFI were balanced 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 the MMS group was 4.20 (P = 0.023). This relationship was confounded, however, by the diagnosis of hematologic tumor or solid tumor (RR = 3.15, 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-related deaths occurred in the NMMS group and one SFI-related death occurred 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 approach to conventional strategies in antifungal prophylaxis for patients receiving HDC.
authors.affiliation: Department of Pharmacy, Saint Louis University Hospital, MO 63110-0250, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Peters
authors.forename: D R
authors.initials: DR
authors.lastname: Adkins
authors.forename: B R
authors.initials: BR
authors.lastname: Harrison
authors.forename: W S
authors.initials: WS
authors.lastname: Velasquez
authors.forename: F R
authors.initials: FR
authors.lastname: Dunphy
authors.forename: P J
authors.initials: PJ
authors.lastname: Petruska
authors.forename: C E
authors.initials: CE
authors.lastname: Bowers
authors.forename: R
authors.initials: R
authors.lastname: Niemeyer
authors.forename: W
authors.initials: W
authors.lastname: McIntyre
authors.forename: D
authors.initials: D
authors.lastname: Vrahnos
authors.forename: S E
authors.initials: SE
authors.lastname: Auberry
authors.forename: G
authors.initials: G
authors.lastname: Spitzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced / Q000188:drug therapy*; D004198:Disease Susceptibility; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D015994:Incidence; D007377:Interleukin-3 / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor