title: Ex vivo expanded peripheral blood progenitor cells provide rapid neutrophil recovery after high-dose chemotherapy in patients with breast cancer.
abstract: Ex vivo expanded peripheral blood progenitor cells (PBPCs) have been proposed as a source of hematopoietic support to decrease or eliminate the period of neutropenia after high-dose chemotherapy. CD34 cells were selected from rhG-CSF mobilized PBPCs from patients with breast cancer and were cultured for 10 days in defined media containing 100 ng/mL each of rhSCF, rhG-CSF, and PEG-rhMGDF in 1 L Teflon bags at 20 000 cells/mL. After culture the cells were washed and reinfused on day 0 of transplantation. On day +1, cohort 1 patients (n = 10) also received an unexpanded CD34-selected PBPC product. These patients engrafted neutrophils (absolute neutrophil count, >500/microL) in a median of 6 (range, 5-14) days. Cohort 2 patients (n = 11), who received expanded PBPCs only, engrafted neutrophils in a median of 8 (range, 4-16) days. In comparison, the median time to neutrophil engraftment in a historical control group of patients (n = 100) was 9 days (range, 7-30 days). All surviving patients are now past the 15-month posttransplantation stage with no evidence of late graft failure. The total number of nucleated cells harvested after expansion culture was shown to be the best predictor of time to neutrophil engraftment, with all patients receiving more than 4 x 10(7) cells/kg, engrafting neutrophils by day 8. No significant effect on platelet recovery was observed in any patient. These data demonstrate that PBPCs expanded under the conditions defined can shorten the time to engraftment of neutrophils compared with historical controls and that the rate of engraftment is related to the dose of expanded cells transplanted.
authors.affiliation: BMT Program, University of Colorado Health Sciences Center, Denver, CO 80262, USA. ian.mcniece@uchsc.edu
authors.forename: I
authors.initials: I
authors.lastname: McNiece
authors.forename: R
authors.initials: R
authors.lastname: Jones
authors.forename: S I
authors.initials: SI
authors.lastname: Bearman
authors.forename: P
authors.initials: P
authors.lastname: Cagnoni
authors.forename: Y
authors.initials: Y
authors.lastname: Nieto
authors.forename: W
authors.initials: W
authors.lastname: Franklin
authors.forename: J
authors.initials: J
authors.lastname: Ryder
authors.forename: A
authors.initials: A
authors.lastname: Steele
authors.forename: J
authors.initials: J
authors.lastname: Stoltz
authors.forename: P
authors.initials: P
authors.lastname: Russell
authors.forename: J
authors.initials: J
authors.lastname: McDermitt
authors.forename: C
authors.initials: C
authors.lastname: Hogan
authors.forename: J
authors.initials: J
authors.lastname: Murphy
authors.forename: E J
authors.initials: EJ
authors.lastname: Shpall
mesh_terms: D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007958:Leukocyte Count; D009367:Neoplasm Staging; D009504:Neutrophils / Q000502:physiology*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012044:Regression Analysis; D019089:Stem Cell Factor / Q000627:therapeutic use; D013926:Thrombopoietin / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D011994:Recombinant Proteins; D019089:Stem Cell Factor; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin