title: Ex vivo expanded unselected peripheral blood: progenitor cells reduce posttransplantation neutropenia, thrombocytopenia, and anemia in patients with breast cancer.
abstract: The safety and efficacy of administering ex vivo expanded peripheral blood progenitor cells (PBPC) to patients with breast cancer who undergo high-dose chemotherapy and PBPC transplantation was investigated. Unselected PBPC were cultured in gas-permeable bags containing 1-L serum-free media, granulocyte colony-stimulating factor, stem cell factor, and pegylated megakaryocyte growth and development factor for 9 days. Cell dose cohorts were assigned to have between 2 and 24 x 10(9) PBPC cultured at 1, 2, or 3 x 10(6) cells/mL. Twenty-four patients received high-dose chemotherapy followed by infusion of the cultured PBPC and at least 5 x 10(6) CD34(+) uncultured cryopreserved PBPC per kilogram. No toxicities resulted from infusions of the ex vivo expanded PBPC. The study patients had shorter times to neutrophil (P =.0001) and platelet (P =.01) recovery and fewer red cell transfusions (P =.02) than 48 historical controls who received the same conditioning regimen and posttransplantation care and at least 5 x 10(6) CD34(+) PBPC per kilogram. Improvements in all these endpoints were significantly correlated with the expanded cell dose. Nine of 24 (38%) patients recovered neutrophil counts above 500/microL by day 5 or 6 after transplantation, whereas none of the controls had neutrophil recovery before the eighth day. Seven (29%) patients had neutropenia for 3 or fewer days, and 9 (38%) patients did not experience neutropenic fevers or require broad-spectrum antibiotics. Therefore, ex vivo expanded PBPC are capable of ameliorating posttransplantation neutropenia, thrombocytopenia, and anemia in patients receiving high-dose chemotherapy.
authors.affiliation: Departments of Medicine and Biostatistics, University of California at Los Angeles, Los Angeles, CA, USA. paquette@ucla.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Paquette
authors.forename: S T
authors.initials: ST
authors.lastname: Dergham
authors.forename: E
authors.initials: E
authors.lastname: Karpf
authors.forename: H J
authors.initials: HJ
authors.lastname: Wang
authors.forename: D J
authors.initials: DJ
authors.lastname: Slamon
authors.forename: L
authors.initials: L
authors.lastname: Souza
authors.forename: J A
authors.initials: JA
authors.lastname: Glaspy
mesh_terms: D000740:Anemia / Q000517:prevention & control*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D002452:Cell Count; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016130:Immunophenotyping; D007902:Length of Stay; D009503:Neutropenia / Q000517:prevention & control*; D017713:Platelet Transfusion; D019089:Stem Cell Factor / Q000494:pharmacology; D013921:Thrombocytopenia / Q000517:prevention & control*; D013926:Thrombopoietin / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D013926:Thrombopoietin