title: K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate.
abstract: OBJECTIVE
  Chronic myeloid leukemia (CML) can be responsive to T-cell-mediated immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM-CSF producing vaccine derived from a CML cell line that expresses several CML-associated antigens. A pilot study was developed to determine if K562/GM-CSF immunotherapy could improve clinical responses to imatinib mesylate (IM) in patients with chronic myeloid leukemia.
  
  
  METHODS
  Patients with chronic phase CML who achieved at least a major cytogeneic response but remained with persistent, measurable disease despite one or more years on imatinib mesylate were eligible. Each was given a series of four vaccines administered in three-week intervals, with or without topical imiquimod, while remaining on a stable dose of imatinib mesylate. CML disease burden was measured serially before and after vaccination.
  
  
  RESULTS
  Nineteen patients were vaccinated, with a median duration of previous imatinib mesylate therapy of 37 (13-53) months. Mean PCR measurements of BCR-ABL for the group declined significantly following the vaccines (P = 0.03). Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable.
  
  
  CONCLUSIONS
  K562/GM-CSF vaccine appears to improve molecular responses in patients on imatinib mesylate, including achieving complete molecular remissions, despite long durations of previous imatinib mesylate therapy.
authors.affiliation: Johns Hopkins Medical Institute, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and St Agnes Hospital, Baltimore, Maryland 21231, USA. bdsmith@jhmi.edu
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Smith
authors.forename: Yvette L
authors.initials: YL
authors.lastname: Kasamon
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Christopher
authors.initials: C
authors.lastname: Gocke
authors.forename: Kathleen
authors.initials: K
authors.lastname: Murphy
authors.forename: Carole B
authors.initials: CB
authors.lastname: Miller
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: Hua-Ling
authors.initials: HL
authors.lastname: Tsai
authors.forename: Lu
authors.initials: L
authors.lastname: Qin
authors.forename: Christina
authors.initials: C
authors.lastname: Chia
authors.forename: Barbara
authors.initials: B
authors.lastname: Biedrzycki
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Harding
authors.forename: Guang Haun
authors.initials: GH
authors.lastname: Tu
authors.forename: Richard
authors.initials: R
authors.lastname: Jones
authors.forename: Kristen
authors.initials: K
authors.lastname: Hege
authors.forename: Hyam I
authors.initials: HI
authors.lastname: Levitsky
mesh_terms: D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage; D001549:Benzamides; D019496:Cancer Vaccines / Q000627:therapeutic use*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000068877:Imatinib Mesylate; D000077271:Imiquimod; D007167:Immunotherapy; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015466:Leukemia, Myeloid, Chronic-Phase; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000628:therapy*; D010865:Pilot Projects; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D000634:Aminoquinolines; D001549:Benzamides; D019496:Cancer Vaccines; D010879:Piperazines; D011743:Pyrimidines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; D000077271:Imiquimod