TY - JOUR
T1 - Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia
AU - Bacigalupo, A.
AU - Piaggio, G.
AU - Figari, O.
AU - Tong, J.
AU - Sogno, G.
AU - Tedone, E.
AU - Sette, A.
AU - Ratto, M. R.
AU - Caciagli, P.
AU - Badolati, G.
AU - Marmont, A.
PY - 1991/8/26
Y1 - 1991/8/26
N2 - The aim of this study was to test whether large amounts of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) are capable of promoting the growth of hemopoietic progenitors from patients with marrow failure. For this purpose 0.1, 100, 1000, 10,000 and 20,000 ng/ml of rhGM-CSF were added to 105 light-density (adherent cell-depleted) bone marrow cells from 9 normal controls and from 52 patients with aplastic anemia, 25 cases of which were transfusion-dependent (Tx-D) aplastic anemia (AA) and 27 of which were transfusion-independent (Tx-I) aplastic anemia (AA). A dose-dependent increase of granulocyte-macrophage colony-forming units (CFU-GM) was observed in healthy donors, from 81 to 247 colonies at 0.1 and 1000 ng/ml of rhGM-CSF, with a plateau thereafter. Tx-I AA patients showed the best increase of CHU-GM in response to colony-stimulating factor, from 0.1 to 32.7 mean colonies at 0.1 and 20,000 ng/ml of rhGM-CSF, and the increment was greater when compared to controls. The ratio of CFU-GM grown from these patients and controls was 1:810 at 0.1 ng/ml of rhGM-CSF and 1:7.9 at 20,000 ng/ml. Eleven patients were studied at diagnosis; there was no in vitro response to rhGM-CSF (0 and 1.8 mean colonies/105 cells at 0.1 and 10,000 ng/ml). Overall, Tx-D AA patients showed minimal increments of CFU-GM growth at very high doses of rhGM-CSF. Two suggesetions come from this study: 1) maturation of CFU-GM from recovering AA patients appears to require larger doses of GM-CSF than normal controls, and 2) very high doses of rhGM-CSF have little or no effect on CFU-GM growt in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure.
AB - The aim of this study was to test whether large amounts of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) are capable of promoting the growth of hemopoietic progenitors from patients with marrow failure. For this purpose 0.1, 100, 1000, 10,000 and 20,000 ng/ml of rhGM-CSF were added to 105 light-density (adherent cell-depleted) bone marrow cells from 9 normal controls and from 52 patients with aplastic anemia, 25 cases of which were transfusion-dependent (Tx-D) aplastic anemia (AA) and 27 of which were transfusion-independent (Tx-I) aplastic anemia (AA). A dose-dependent increase of granulocyte-macrophage colony-forming units (CFU-GM) was observed in healthy donors, from 81 to 247 colonies at 0.1 and 1000 ng/ml of rhGM-CSF, with a plateau thereafter. Tx-I AA patients showed the best increase of CHU-GM in response to colony-stimulating factor, from 0.1 to 32.7 mean colonies at 0.1 and 20,000 ng/ml of rhGM-CSF, and the increment was greater when compared to controls. The ratio of CFU-GM grown from these patients and controls was 1:810 at 0.1 ng/ml of rhGM-CSF and 1:7.9 at 20,000 ng/ml. Eleven patients were studied at diagnosis; there was no in vitro response to rhGM-CSF (0 and 1.8 mean colonies/105 cells at 0.1 and 10,000 ng/ml). Overall, Tx-D AA patients showed minimal increments of CFU-GM growth at very high doses of rhGM-CSF. Two suggesetions come from this study: 1) maturation of CFU-GM from recovering AA patients appears to require larger doses of GM-CSF than normal controls, and 2) very high doses of rhGM-CSF have little or no effect on CFU-GM growt in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure.
KW - Aplastic anemia
KW - Colony-stimulating factor
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M3 - Article
C2 - 1868897
AN - SCOPUS:0025908933
VL - 19
SP - 829
EP - 832
JO - Experimental Hematology
JF - Experimental Hematology
SN - 0301-472X
IS - 8
ER -