EFFECTS OF SHORT-TERM IN-VIVO ADMINISTRATION OF 6-CSF ON BONE-MARROW PRIOR TO HARVESTING

The brief administration of G-CSF to previously treated solid tumor pa tients has a positive impact on the overall cellularity and progenitor cell content of harvested bone marrow. Fifty-seven patients, fully re covered from therapy and growth factor support, had approximately 500 mi of steady-state marrow harvested as outpatients under local anesthe sia. Each patient then received 5 mu g/kg of G-CSF every 12 hours subc utaneously for either 24 hours (21 patients), 36 hours (20 patients), or 48 hours (16 patients) just before harvesting 500 mt of activated b one marrow. Bone marrow cellularity (x10(6)/mL) increased from a stead y-state mean of 10.7 (+/- 0.9) to 25.7 (+/- 2.8) after 24 hours, 9.3 ( +/- 0.7) to 29 (+/- 2.5) after 36 hours, and 9.6 (+/- 0.7) to 28.4 (+/ - 2.5) after 48 hours. Although the percentage of CD34(+) cells did no t significantly change in stimulated marrow, the total number of CD34( +) cells (x10(6)) collected increased from 34 (+/- 6.3) to 52 (+/- 6.6 ) after two injections, 28 (+/- 3.6) to 65 (+/- 8.5) after three injec tions, and 28 (+/- 5.4) to 75 (+/- 18) after four injections of G-CSF. Further phenotyping demonstrated significant increases in CD34(+)HDL- DR(+) cells with ail three schedules relative to steady-state marrow. There were no changes in the total number of CD34(+)HLD-DR(+) cells af ter two and four shots; however, this population increased from 10 x 1 0(6) in steady-state marrow to 23 x 10(6) (P = 0.012) after three inje ctions. Analysis of peripheral blood indicated a statistically signifi cant increase in the circulating white count, but more interestingly, there were significant increases in the number of CD34(+) cells x 10(4 )/mL, suggesting the onset of mobilization. Steady-state blood contain ed a mean of 0.86 x 10(4)/mL CD34(+) cells, which increased to 4.37 x 10(4)/mL, 7.43 x 10(4)/mL, and 8.62 x 10(4)/mL after two, three, and f our injections, respectively-levels of CD34(+) cells that are comparab le to steady-state marrow. Reinfusion of a median of 1.6 x 10(6) activ ated CD34(+) cells/kg resulted in the recovery of >100/mm(3) neutrophi ls and >20,000 platelets by days 9 and 19, respectively, which was fas ter than our previous patients who received steady-state marrow, and c omparable to our patients who received mobilized peripheral stem cells .