Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors

C. Carlo-Stella, A. Tabilio, E. Regazzi, D. Garau, R. La Tagliata, S. Trasarti, C. Andrizzi, M. Vignetti, G. Meloni

Research output: Contribution to journalArticlepeer-review


Since reduced marrow cellularity and prolonged pancytopenia following autologous bone marrow transplantation (ABMT) have been frequently observed in patients with acute myelogenous leukemia (AML) included in the AML10 GIMEMA/EORTC trial, the question was raised to what extent hematopoietic and microenvironmental progenitor cells were involved in these patients. Marrow hematopoietic progenitors were investigated by a short-term methylcellulose assay quantitating multipotent CFU-Mix, erythroid BFU-E and granulocyte-macrophage CFU-GM, as well as a long-term assay quantitating long-term culture-initiating cells (LTC-IC). The marrow microenvironment was studied by evaluating the incidence of fibro-blastoid progenitors (CFU-F) and the capacity of stromal layers to support allogeneic hematopoietic progenitors. As compared to normal controls (n = 57), AML patients (n = 26) showed a statistically significant reduction of the mean (± s.e.m.) number of CFU-Mix (5.3 ± 0.6 vs 0.8 ± 0.2, P ≤ 0.0001), BFU-E (68 ± 5 vs 20 ± 4, P ≤ 0.0001), CFU-GM (198 ± 11 vs 144 ± 15, P ≤ 0.008), and LTC-IC (302 ± 46 vs 50 ± 8, P ≤ 0.001). The mean (± s.e.m.) incidence of marrow CFU-F was not significantly reduced as compared to normal controls (48 ± 6 vs 52 ± 7, P ≤ 0.73). Seventeen AML stromal layers were tested for their capacity to support the growth of allogeneic hematopoietic progenitors. Seven samples failed to support any progenitor cell growth, seven had a significantly lower supportive activity as compared to normal stromal layers (13 ± 5 vs 249 ± 56, P ≤ 0.002), whereas three cultures could not be analyzed due to contamination. In conclusion, induction and consolidation regimens used in AML patients of the AML10 protocol induce a markedly defective in vitro growth of primitive hematopoietic progenitors and a severe functional defect of marrow stroma. The association of hematopoietic with microenvironmental damage might play a key role in the delayed hematopoietic regeneration observed following ABMT in patients of the AML10 trial.

Original languageEnglish
Pages (from-to)465-471
Number of pages7
JournalBone Marrow Transplantation
Issue number6
Publication statusPublished - Sep 2 1997


  • Acute myelogenous leukemia
  • Chemotherapy
  • Hematopoietic engraftment
  • Hematopoietic progenitors
  • LTC-IC
  • Microenvironmental progenitors

ASJC Scopus subject areas

  • Hematology
  • Transplantation


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