Objective. The aim of this study was to evaluate the capacity of defibrotide in enhancing cytokine-induced hematopoietic mobilization in rhesus monkeys. Materials and Methods. Animals received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 100 μg/kg/day SC for 5 days) and, after a 4- to 6-week washout period, were remobilized with defibrotide (15 mg/kg/hour continuous intravenous for 5 days) plus rhG-CSF. Hematopoietic mobilization was evaluated by complete blood counts, differential counts, as well as frequency and absolute numbers of colony-forming cells (CFCs), high-proliferative potential CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). Results. Compared to baseline values, rhG-CSF increased circulating CFCs, HPP-CFCs, and LTC-ICs by 158-, 125-, and 67-fold, respectively; the same figures for defibrotide/rhG-CSF were 299-, 1452-, and 295-fold, respectively. Defibrotide/rhG-CSF treatment compared to rhG-CSF alone increased CFCs, HPP-CFCs, and LTC-ICs by 1.4- (35,089 vs 25,825, p≤0.02), 6- (4358 vs 748, p≤0.02), and 5-fold (884 vs 168, p≤0.04), respectively. We then evaluated the effects of a 2-day defibrotide treatment associated with a 5-day rhG-CSF treatment. Compared to rhG-CSF, defibrotide/rhG-CSF increased the mobilization of CFCs, HPP-CFCs, and LTC-ICs by 2- (31,128 vs 15,527, p≤0.05), 8- (5361 vs 660, p≤0.01), and 8-fold (954 vs 119, p≤0.01), respectively. Conclusions. Our data demonstrate that in nonhuman primates: 1) defibrotide enhances rhG-CSF-elicited mobilization of primitive and committed progenitors; and 2) a 2-day defibrotide injection is as effective as a 5-day injection.

Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with Defibrotide and recombinant human granulocyte colony-stimulating factor / C. Carlo-Stella, M. Di Nicola, P. Longoni, R. Milani, M. Milanesi, A. Guidetti, K. Haanstra, M. Jonker, L. Cleris, M. Magni, F. Formelli, A.M. Gianni. - In: EXPERIMENTAL HEMATOLOGY. - ISSN 0301-472X. - 32:1(2004), pp. 68-75. [10.1016/j.exphem.2003.09.022]

Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with Defibrotide and recombinant human granulocyte colony-stimulating factor

C. Carlo-Stella;A. Guidetti;A.M. Gianni
2004

Abstract

Objective. The aim of this study was to evaluate the capacity of defibrotide in enhancing cytokine-induced hematopoietic mobilization in rhesus monkeys. Materials and Methods. Animals received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 100 μg/kg/day SC for 5 days) and, after a 4- to 6-week washout period, were remobilized with defibrotide (15 mg/kg/hour continuous intravenous for 5 days) plus rhG-CSF. Hematopoietic mobilization was evaluated by complete blood counts, differential counts, as well as frequency and absolute numbers of colony-forming cells (CFCs), high-proliferative potential CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). Results. Compared to baseline values, rhG-CSF increased circulating CFCs, HPP-CFCs, and LTC-ICs by 158-, 125-, and 67-fold, respectively; the same figures for defibrotide/rhG-CSF were 299-, 1452-, and 295-fold, respectively. Defibrotide/rhG-CSF treatment compared to rhG-CSF alone increased CFCs, HPP-CFCs, and LTC-ICs by 1.4- (35,089 vs 25,825, p≤0.02), 6- (4358 vs 748, p≤0.02), and 5-fold (884 vs 168, p≤0.04), respectively. We then evaluated the effects of a 2-day defibrotide treatment associated with a 5-day rhG-CSF treatment. Compared to rhG-CSF, defibrotide/rhG-CSF increased the mobilization of CFCs, HPP-CFCs, and LTC-ICs by 2- (31,128 vs 15,527, p≤0.05), 8- (5361 vs 660, p≤0.01), and 8-fold (954 vs 119, p≤0.01), respectively. Conclusions. Our data demonstrate that in nonhuman primates: 1) defibrotide enhances rhG-CSF-elicited mobilization of primitive and committed progenitors; and 2) a 2-day defibrotide injection is as effective as a 5-day injection.
Settore MED/06 - Oncologia Medica
2004
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/19864
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