EFFECT OF RECOMBINANT HUMAN STEM-CELL FACTOR ON MAFOSFAMIDE-TREATED BONE-MARROW CLONOGENIC CELLS

The availability of early-acting cytokines could allow the establishme nt of new approaches to chemical marrow purging. It was the aim of the present study to investigate the capability of recombinant human stem cell factor (SCF) in combination with other growth factors to support the in vitro growth of mafosfamide-treated progenitor cells such as m ixed colony forming units (CFU-GEMM), erythroid burst forming units (B FU-E) and granulocyte-macrophage CFU (CFU-GM). When marrow cells were incubated (30 min, 37-degrees-C) with increasing doses of mafosfamide (30-120 mug/ml) a statistically significant (p less-than-or-equal-to . 05), dose-dependent suppression of colony growth was observed. Additio n of SCF (50 ng/ml) to marrow cultures stimulated with the standard mi xture of growth factors (interleukin 3 or IL-3, granulocyte-macrophage colony stimulating factor or GM-CSF, and erythropoietin or Epo) signi ficantly increased the mean (+/- SD) concentration of mafosfamide indu cing 95% inhibition of CFU-GM (106 +/- 17 versus 130 +/- 29, p less-th an-or-equal-to .0005), but not granulocyte/erythroid/macrophage/megaka ryocyte CFU (CFU-GEMM) (85 +/- 4 versus 90 +/- 1,p less-than-or-equal- to .1) and BFU-E (90 +/- 5 versus 92 +/- 5,p less-than-or-equal-to .1) . SCF induces a dose-dependent, statistically significant enhancement of colony formation by CD34+, mafosfamide-treated cells. As shown by s ingle colony transfer experiments, mafosfamide-resistant clones promot ed by SCF have a significantly higher replating capacity as compared w ith mafosfamide-resistant clones grown without SCF. In conclusion, SCF -enhanced proliferation of mafosfamide-treated, CD34-enriched progenit or cells further confirm that SCF is an early-acting cytokine that pre ferentially stimulates the growth of immature hematopoietic progenitor s. These data might have relevant implications not only in view of ''h yper-purging strategies,'' but also for the clinical management of pat ients undergoing autologous bone marrow transplant (ABMT).