title: Breast tumor contamination of PBSC harvests: tumor depletion by positive selection of CD34(+) cells.
abstract: BACKGROUND
  Positive selection of CD34(+) cells may reduce or eliminate tumor cells contaminating PBSC harvests of breast cancer (BrCa) patients. However, to assess tumor purging accurately methods may be needed that are of higher sensitivity than standard immunocytochemistry (ICC) assays.
  
  
  METHODS
  BrCa-cell depletion, resulting from CD34(+) cell selection, was evaluated using a novel, highly sensitive assay based upon immunomagnetic enrichment with ICC detection in 36 BrCa patients undergoing highdose chemotherapy with autologous PBSC support.
  
  
  RESULTS
  The prevalence of BrCa-cell contamination was significantly lower (P = 0.0078) in selected CD34(+) cell fractions (17/35, 49%) from apheresis collections compared with CD34(-) cell fractions (25/35, 71%). In 8/34 (24%) patients, BrCa cells were detected in CD34(-) cell fractions, but not in paired CD34(+) cell fractions. Significantly lower total numbers (P < 0.0005) of BrCa cells were enumerable in CD34(+) cell fractions compared with corresponding apheresis harvests. The median total BrCa-cell content of selected CD34(+) cell fractions with measurable contamination was 22 BrCa cells (range, 6-73 BrCa cells), compared with 3297 BrCa cells (range, 10-98 400 BrCa cells) in apheresis harvests. The median log depletion of BrCa cells achieved by positive CD34(+) cell selection in specimens with detectable contamination both before and after selection was 2.2 (range, 1.7-4.0). Total pre-selection BrCa cell number was significantly predictive (P = 0.004) of residual detectable post-selection contamination.
  
  
  CONCLUSIONS
  Positive CD34(+) cell selection is an effective tumor purging strategy. The prevalence of PBSC contamination in BrCa patients is substantially higher than formerly appreciated.
authors.affiliation: Nexell Therapeutics Inc., Irvine, California 92618-1605, USA.
authors.forename: J
authors.initials: J
authors.lastname: Burgess
authors.forename: B
authors.initials: B
authors.lastname: Mills
authors.forename: M
authors.initials: M
authors.lastname: Griffith
authors.forename: V
authors.initials: V
authors.lastname: Mansour
authors.forename: C H
authors.initials: CH
authors.lastname: Weaver
authors.forename: L S
authors.initials: LS
authors.lastname: Schwartzberg
authors.forename: E L
authors.initials: EL
authors.lastname: Snyder
authors.forename: D S
authors.initials: DS
authors.lastname: Krause
authors.forename: S
authors.initials: S
authors.lastname: Yanovich
authors.forename: M
authors.initials: M
authors.lastname: Prilutskaya
authors.forename: T
authors.initials: T
authors.lastname: Umiel
authors.forename: T J
authors.initials: TJ
authors.lastname: Moss
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34 / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D002452:Cell Count; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D018189:Immunomagnetic Separation / Q000379:methods*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000276:immunology* / Q000473:pathology; D011237:Predictive Value of Tests; D015203:Reproducibility of Results
chemical_list: D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; D015415:Biomarkers