Clonogenic potential and phenotypic analysis of CD34+ cells mobilized by different chemotherapy regimens

Haematologica. 1999 Sep;84(9):771-8.

Abstract

Background and objective: Since limited data concerning quantitative and qualitative differences of CD34+ cells collected after different mobilization schedules are available, we investigated phenotype, proliferative capacity and primitive progenitor cell content of CD34+ cells mobilized with four different regimens.

Design and methods: The number, phenotype, and progenitor cell content of CD34+ cells were investigated in 46 patients mobilized with cyclophosphamide (CY) 7 g/m(2) plus granulocyte colony-stimulating factor (G-CSF, 5 microg/kg) (CY7+G-CSF) (n=16), CY 4 g/m(2) plus G-CSF (CY4+G-CSF) (n=8), IVE [ifosphamide (2.5 g/m(2) for 3 d), etoposide (150 mg/m(2) for 3 d), epirubicin (100 mg/m(2) on day 1)] plus G-CSF (IVE+G-CSF) (n=9), or G-CSF (10 microg/kg) alone (n=13).

Results: The number of CD34+ cells collected per liter of processed blood was significantly higher in the CY7+G-CSF group than in the CY4+G-CSF and G-CSF groups (p </= .005), but not the IVE+G-CSF group. As compared to patients in the CY4+G-CSF group, those mobilized with CY7+G-CSF and IVE+G-CSF produced significantly lower percentages of CD34+ cells lacking CD38, CD33, CD45RA, and HLA-DR (p </= .016, at least). In addition, CY4+G-CSF mobilized CD34+ cells had a significantly higher plating efficiency than the cells mobilized in other ways (p </= r .036). In the G-CSF group, colony-forming cells and long-term culture-initiating cells were significantly lower than in the CY groups (p </= .0014 and </= 013, respectively).

Interpretation and conclusions: Our data demonstrate that: (i) different mobilization regimens allow the collection of CD34+ cells with distinct phenotypic and proliferative features; (ii) evaluation of the absolute number of CD34+ cells by itself is not a reliable indicator of the clonogenic content of blood mobilized with different chemotherapy regimens; (iii) because of the substantial impact that chemotherapy regimens have on the quantity and quality of collected CD34+ cells, anticancer effects and optimal blood progenitor cell yields should be evaluated for each chemotherapy schedule.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Colony-Forming Units Assay
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Drug Synergism
  • Epirubicin / administration & dosage
  • Epirubicin / pharmacology
  • Etoposide / administration & dosage
  • Etoposide / pharmacology
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / pharmacology
  • Immunophenotyping
  • Leukapheresis
  • Leukocyte Count / drug effects
  • Male
  • Neoplasms / therapy

Substances

  • Granulocyte Colony-Stimulating Factor
  • Epirubicin
  • Etoposide
  • Cyclophosphamide
  • Ifosfamide