CELL-CYCLE KINETICS OF HEMATOPOIESIS BEFORE AND AFTER IN-VIVO ADMINISTRATION OF GM-CSF IN REFRACTORY-ANEMIA - EVIDENCE FOR A SHORTENING OF THE GRANULOCYTE RELEASE TIME

GM-CSF administration to patients with refractory anemia (RA) induces an increase in neutrophils and eosinophils. We studied cell kinetic me chanisms underlying this observation using clonogenic assays and in vi vo iododeoxyuridine labeling of bone marrow cells. Cell cycle kinetics were studied in three patients before and during GM-CSF administratio n (two daily subcutaneous injections of 54 or 108 mu g). No consistent effect on the relative number of bone marrow CFU-GM was noticed. The DNA synthesis time and potential doubling time of low-density bone mar row cells remained essentially the same. A slight decrease (1.5-3.7%) in labeling index was found, originating from the myelo(-mono)cytic li neage. In all three patients the release time of labeled granulocytes from the bone marrow into the peripheral blood was shortened (before G M-CSF treatment 5-7 days and during GMCSF 3-4 days). Cell cycle kineti cs of CD34(+) cells were studied in order to obtain kinetic informatio n on immature precursor and progenitor cells. The DNA synthesis time o f the CD34(+) cells was shortened during GM-CSF therapy, resulting in a shorter potential doubling time. GM-CSF administration to patients w ith RA results in a rise in granulocytes that might be due partly to a n accelerated release of granulocytes from the bone marrow compartment into the circulating blood and partly to an increased proliferative a ctivity of the immature precursor and progenitor cells.