title: Phenotypic and functional analysis of dendritic cells and clinical outcome in patients with high-risk melanoma treated with adjuvant granulocyte macrophage colony-stimulating factor.
abstract: OBJECTIVE
  Granulocyte macrophage colony-stimulating factor (GM-CSF) can induce differentiation of dendritic cells (DCs) in preclinical models. We hypothesized that GM-CSF-stimulated DC differentiation may result in clinical benefit in patients with high-risk melanoma.
  
  
  METHODS
  We conducted a prospective trial in patients with high-risk (stage III B/C, IV), resected melanoma, with GM-CSF 125 microg/m(2)/d administered for 14 days every 28 days. Patients underwent clinical restaging every four cycles, with DC analysis performed at baseline and at 2, 4, 8, and 12 weeks.
  
  
  RESULTS
  Of 42 patients enrolled, 39 were assessable for clinical outcome and DC analysis. Median overall survival was 65 months (95% CI, 43 to 67 months) and recurrence-free survival was 5.6 months (95% CI, 3 to 11 months). GM-CSF treatment caused an increase in mature DCs, first identified after 2 weeks of treatment, normalizing by 4 weeks. Patients with decreased DCs at baseline had significant increases in DC number and function compared with those with "normal" parameters at baseline. No change was observed in the number of myeloid-derived suppressor cells (MDSCs). Early recurrence (< 90 days) correlated with a decreased effect of GM-CSF on host DCs, compared with late or no (evidence of) recurrence.
  
  
  CONCLUSIONS
  GM-CSF treatment was associated with a transient increase in mature DCs, but not MDSCs. Greater increase of DCs was associated with remission or delayed recurrence. The prolonged overall survival observed warrants further exploration.
authors.affiliation: H. Lee Moffitt Cancer Center, Tampa, FL, USA. adaud@medicine.ucsf.edu
authors.forename: Adil I
authors.initials: AI
authors.lastname: Daud
authors.forename: Noweeda
authors.initials: N
authors.lastname: Mirza
authors.forename: Brianna
authors.initials: B
authors.lastname: Lenox
authors.forename: Stephanie
authors.initials: S
authors.lastname: Andrews
authors.forename: Patricia
authors.initials: P
authors.lastname: Urbas
authors.forename: Gui X
authors.initials: GX
authors.lastname: Gao
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
authors.forename: Adam I
authors.initials: AI
authors.lastname: Riker
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Deconti
authors.forename: Dmitry
authors.initials: D
authors.lastname: Gabrilovich
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor