Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia

A. Bacigalupo, G. Piaggio, O. Figari, J. Tong, G. Sogno, E. Tedone, A. Sette, M. R. Ratto, P. Caciagli, G. Badolati, A. Marmont

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)829-832
Number of pages4
JournalExperimental Hematology
Volume19
Issue number8
Publication statusPublished - Aug 26 1991

Keywords

  • Aplastic anemia
  • Colony-stimulating factor

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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