Effects of prior therapy on the in vitro proliferative potential of stem cell factor plus filgrastim-mobilized CD34-positive progenitor cells Journal Article


Authors: Shapiro, F.; Yao, T. J.; Moskowitz, C.; Reich, L.; Wuest, D. L.; Heimfeld, S.; McNiece, I. K.; Gabrilove, J.; Nimer, S.; Moore, M. A. S.
Article 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 104 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 (x l05) 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.
Keywords: cancer chemotherapy; human tissue; human cell; cancer radiotherapy; cell proliferation; cell division; cd34 antigen; stem cell factor; erythropoietin; hematopoietic stem cell transplantation; nonhodgkin lymphoma; lymphoma, non-hodgkin; recombinant proteins; cell subpopulation; hematopoietic stem cells; interleukin-6; area under curve; hematopoietic stem cell; recombinant granulocyte colony stimulating factor; colony-forming units assay; antigens, cd34; hematopoietic stem cell mobilization; filgrastim; leukapheresis; apheresis; interleukin-3; humans; human; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 3
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 1997-09-01
Start Page: 1571
End Page: 1578
Language: English
PUBMED: 9815845
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus