EFFECTS OF PRIOR THERAPY ON THE IN-VITRO PROLIFERATIVE POTENTIAL OF STEM-CELL FACTOR PLUS FILGRASTIM-MOBILIZED CD34-POSITIVE PROGENITOR CELLS

The quantity of hematopoietic progenitors in an apheresis collection i s defined by the number of CD34(+) cells or granulocyte macrophage col ony-forming units present, These parameters are believed to give rough ly equivalent information on graft quality, We here report that the li t vitro proliferative potential of r-metHuSCF (stem cell factor) plus filgrastim (granulocyte colony-stimulating factor; r-metHuG-CSF) mobil ized peripheral blood (PB) CD34(+) cells obtained from previously heav ily 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 presen ce of either r-metHuSCF, IL-3, IL-6, filgrastim (S36G), or S36G plus e rythropoietin (S36GE) with a weekly exchange of media and cytokines wi th reestablishment of culture at the starting cell concentration (Delt a assay) and enumeration of progenitors, Starting with 4 x 10(4) CD34( +) cells from apheresis samples from patients who had received <10 cyc les of prior chemotherapy, progenitors were detectable in culture at 4 weeks 81% of the time as compared to 14% with CD34(+) cells from pati ents who had received >10 cycles and 5% for >10 cycles plus radiothera py, The total number of progenitors generated over the duration of cul ture (area under the curve) was calculated using the trapezoidal rule as a novel measure of the proliferative potential of the enriched PB C D34(+) cell population, The median area under the curve of CD34(+) cel ls from patients receiving <10 cycles of prior chemotherapy was 7.4 an d 5.7 (x10(5)) using S36G or S36GE, respectively, 1.8 and 1.9 if the p atients received >10 cycles of prior chemotherapy, and 1.4 and 1.2 if the patients received >10 cycles of prior chemotherapy plus radiothera py (P < 0.001), These data show that prior therapy impacts on the qual ity of PB CD34(+) cells as measured by their ability to generate commi tted progenitors over a number of weeks in liquid culture.