title: Effects of prior therapy on the in vitro proliferative potential of stem cell factor plus filgrastim-mobilized CD34-positive progenitor cells.
abstract: The quantity of hematopoietic progenitors in an apheresis collection is defined by the number of CD34(+) cells or granulocyte macrophage colony-forming units present. These parameters are believed to give roughly equivalent information on graft quality. We here report that the in vitro proliferative potential of r-metHuSCF (stem cell factor) plus filgrastim (granulocyte colony-stimulating factor; r-metHuG-CSF) mobilized peripheral blood (PB) CD34(+) cells obtained from previously heavily treated non-Hodgkin's lymphoma patients inversely correlates with extent of prior therapy. CD34(+) cells were enriched using the CellPro Ceprate system and placed in liquid culture for 4 weeks in the presence of either r-metHuSCF, IL-3, IL-6, filgrastim (S36G), or S36G plus erythropoietin (S36GE) with a weekly exchange of media and cytokines with reestablishment of culture at the starting cell concentration (Delta assay) and enumeration of progenitors. Starting with 4 x 10(4) CD34(+) cells from apheresis samples from patients who had received <10 cycles of prior chemotherapy, progenitors were detectable in culture at 4 weeks 81% of the time as compared to 14% with CD34(+) cells from patients who had received >10 cycles and 5% for >10 cycles plus radiotherapy. The total number of progenitors generated over the duration of culture (area under the curve) was calculated using the trapezoidal rule as a novel measure of the proliferative potential of the enriched PB CD34(+) cell population. The median area under the curve of CD34(+) cells from patients receiving <10 cycles of prior chemotherapy was 7.4 and 5.7 (x10(5)) using S36G or S36GE, respectively, 1.8 and 1.9 if the patients received >10 cycles of prior chemotherapy, and 1.4 and 1.2 if the patients received >10 cycles of prior chemotherapy plus radiotherapy (P < 0.001). These data show that prior therapy impacts on the quality of PB CD34(+) cells as measured by their ability to generate committed progenitors over a number of weeks in liquid culture.
authors.affiliation: James Ewing Laboratory of Developmental Hematopoiesis, Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: F
authors.initials: F
authors.lastname: Shapiro
authors.forename: T J
authors.initials: TJ
authors.lastname: Yao
authors.forename: C
authors.initials: C
authors.lastname: Moskowitz
authors.forename: L
authors.initials: L
authors.lastname: Reich
authors.forename: D L
authors.initials: DL
authors.lastname: Wuest
authors.forename: S
authors.initials: S
authors.lastname: Heimfeld
authors.forename: I K
authors.initials: IK
authors.lastname: McNiece
authors.forename: J
authors.initials: J
authors.lastname: Gabrilove
authors.forename: S
authors.initials: S
authors.lastname: Nimer
authors.forename: M A
authors.initials: MA
authors.lastname: Moore
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D019540:Area Under Curve; D002455:Cell Division; D003114:Colony-Forming Units Assay; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007937:Leukapheresis; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018952:Antigens, CD34; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim; C105861:ancestim