BOTH CYCLING AND NONCYCLING PRIMITIVE PROGENITORS CONTINUE TO BE MOBILIZED INTO THE CIRCULATION DURING THE LEUKAPHERESIS OF PATIENTS PRETREATED WITH CHEMOTHERAPY AND G-CSF

Colony-forming cells (CFC) and long-term culture-initiating cells (LTC -IC) include a spectrum of progenitor types whose potential contributi ons to the haemopoietic recovery seen in patients transplanted with mo bilized peripheral blood progenitor cells (PBPC) remains unclear. We e valuated both the number and cycling status of the circulating LTC-IC and CFC harvested from 12 patients treated with chemotherapy and G-CSF using a modified 6-week LTC-IC assay, The frequency of the LTC-IC and CFC in the mobilized PB samples were increased 45- and 750-fold, resp ectively. Interestingly, comparison of these values for PB samples, ta ken just prior to the start of the leukapheresis, with the progenitor content of the 3 h harvest, showed that, on average, the leukapheresis product contained 19 times more LTC-IC (P<0.01) than had been detecta ble in the entire blood volume of the patients at the start of the col lection, whereas the number of CFC collected was approximately the sam e as the number in the initial circulating pool of PBPC. Cycling studi es showed many of the LTC-IC in the apheresis collections to be prolif erating although not more so than in the steady-state marrow LTC-IC co mpartment (i.e. per cent kill of mobilized LTC-IC after 16 h in H-3-Td r = 70 +/- 8%, n = 9), On the other hand, the majority of the CFC in t he apheresis collections were initially quiescent (per cent kill after 16 h in H-3-Tdr = 37 +/- 6%, n = 12). These findings demonstrate the rapidity with which a primitive subset of LTS-IC may enter the circula tion during the early phase of rebound haemopoiesis induced by chemoth erapy plus G-CSF and provide evidence of differences in the mechanisms regulating LTC-IC and CFC mobilization.