TY - JOUR
T1 - Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors
AU - Carlo-Stella, C.
AU - Tabilio, A.
AU - Regazzi, E.
AU - Garau, D.
AU - La Tagliata, R.
AU - Trasarti, S.
AU - Andrizzi, C.
AU - Vignetti, M.
AU - Meloni, G.
PY - 1997/9/2
Y1 - 1997/9/2
N2 - 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.
AB - 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.
KW - Acute myelogenous leukemia
KW - Chemotherapy
KW - Hematopoietic engraftment
KW - Hematopoietic progenitors
KW - LTC-IC
KW - Microenvironmental progenitors
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M3 - Article
C2 - 9313879
AN - SCOPUS:0030815188
VL - 20
SP - 465
EP - 471
JO - Bone Marrow Transplantation
JF - Bone Marrow Transplantation
SN - 0268-3369
IS - 6
ER -