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: F Shapiro, T J Yao, C Moskowitz, L Reich, D L Wuest, S Heimfeld, I K McNiece, J Gabrilove, S Nimer, M A Moore
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 3 Issue 9 Pg. 1571-8 (Sep 1997) ISSN: 1078-0432 [Print] United States
• PMID: 9815845 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD34
• Interleukin-3
• Interleukin-6
• Recombinant Proteins
• Stem Cell Factor
• Granulocyte Colony-Stimulating Factor
• Filgrastim
• ancestim

Topics

• Antigens, CD34 (analysis)
• Area Under Curve
• Cell Division
• Colony-Forming Units Assay
• Filgrastim
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Hematopoietic Stem Cell Mobilization
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (drug effects)
• Humans
• Interleukin-3 (pharmacology)
• Interleukin-6 (pharmacology)
• Leukapheresis
• Lymphoma, Non-Hodgkin (drug therapy, pathology, therapy)
• Recombinant Proteins (pharmacology)
• Stem Cell Factor (analogs & derivatives, pharmacology)