title: Postoperative adjuvant dendritic cell-based immunotherapy in patients with relapsed glioblastoma multiforme.
abstract: OBJECTIVE
  To investigate the therapeutic role of adjuvant vaccination with autologous mature dendritic cells (DC) loaded with tumor lysates derived from autologous, resected glioblastoma multiforme (GBM) at time of relapse.
  
  
  METHODS
  Fifty-six patients with relapsed GBM (WHO grade IV) were treated with at least three vaccinations. Children and adults were treated similarly in three consecutive cohorts, with progressively shorter vaccination intervals per cohort. Feasibility and toxicity were assessed as well as effect of age, extent of resection, Karnofsky Performance Score, and treatment cohort on the progression-free (PFS) and overall survival (OS) using univariable and multivariable analysis.
  
  
  RESULTS
  Since the prevaccine reoperation, the median PFS and OS of the total group was 3 and 9.6 months, respectively, with a 2-year OS of 14.8%. Total resection was a predictor for better PFS both in univariable analysis and after correction for the other covariates. For OS, younger age and total resection were predictors of a better outcome in univariable analysis but not in multivariable analysis. A trend to improved PFS was observed in favor of the faster DC vaccination schedule with tumor lysate boosting. Vaccine-related edema in one patient with gross residual disease before vaccination was the only serious adverse event.
  
  
  CONCLUSIONS
  Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.
authors.affiliation: Department of Neurosurgery, Catholic University of Leuven, Leuven, Belgium. steven.devleeschouwer@uz.kuleuven.ac.be
authors.forename: Steven
authors.initials: S
authors.lastname: De Vleeschouwer
authors.forename: Steffen
authors.initials: S
authors.lastname: Fieuws
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Frank
authors.initials: F
authors.lastname: Van Calenbergh
authors.forename: Johannes
authors.initials: J
authors.lastname: Van Loon
authors.forename: Jan
authors.initials: J
authors.lastname: Goffin
authors.forename: Raf
authors.initials: R
authors.lastname: Sciot
authors.forename: Guido
authors.initials: G
authors.lastname: Wilms
authors.forename: Philippe
authors.initials: P
authors.lastname: Demaerel
authors.forename: Monika
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Niels
authors.initials: N
authors.lastname: Soerensen
authors.forename: Johannes E A
authors.initials: JE
authors.lastname: Wolff
authors.forename: Sabine
authors.initials: S
authors.lastname: Wagner
authors.forename: Eckhart
authors.initials: E
authors.lastname: Kaempgen
authors.forename: Stefaan W
authors.initials: SW
authors.lastname: Van Gool
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002648:Child; D003713:Dendritic Cells / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000628:therapy*; D011184:Postoperative Period
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines