Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia.
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 10(5) 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 CFU-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/10(5) 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 suggestions 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 growth in AA patients. This may be relevant for clinical studies designed to improve hemopoiesis in patients with marrow failure.
Bacigalupo
A
A
Department of Hematology, BMT Unit, San Martino Hospital, Genoa, Italy.
Piaggio
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G
Figari
O
O
Tong
J
J
Sogno
G
G
Tedone
E
E
Sette
A
A
Ratto
M R
MR
Caciagli
P
P
Badolati
G
G
D000328:Adult; D000741:Anemia, Aplastic / Q000503:physiopathology* / Q000628:therapy; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001803:Blood Transfusion; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013997:Time Factors
D000961:Antilymphocyte Serum; D016178:Granulocyte-Macrophage Colony-Stimulating Factor