IN-VITRO EFFECT OF STEM-CELL FACTOR ON HUMAN CLONOGENIC MARROW PROGENITORS AFTER MYELOABLATIVE TREATMENTS

Abnormal hematopoiesis, including a deficiency of marrow progenitors a nd particularly of erythroid progenitors, has been described after aut ologous stem cell transplantation (ASCT), persisting for several years . In order to explain this deficiency, a resistance of marrow progenit ors to stem cell factor (SCF) after ASCT was investigated. Marrow samp les were harvested from pregraft patients at graft collection prior to ASCT, transplanted patients 6-24 months after high-dose therapy and c ontrol patients. CD34(+) cells were cultured in a serum-free clonogeni c assay with increasing doses of SCE. The clonogenic efficiency withou t SCF was lower for BFU-E in treated groups than in controls, whereas it was not different for CFU-GM. With increasing doses of SCF a dose-d ependent effect was found on the numbers of both CFU-GM and BFU-E in a ll groups, although the maximal number of BFU-E remained lower in trea ted groups. However, the SCF dose that induced 50% of maximal BFU-E gr owth (D-50) was similar in all groups. Furthermore, a dose-dependent e ffect on the size of BFU-E was found in all groups, with no difference in the proportion of large colonies. Thus, clonogenic erythroid proge nitors from patients who have received myelotoxic treatments remain se nsitive to SCF, with no evidence for a chemotherapy-related resistance .