Carmelo Carlo-Stella، نويسنده , , Massimo Di Nicola، نويسنده , , Paolo Longoni، نويسنده , , Raffaella Milani، نويسنده , , Marco Milanesi، نويسنده , , Anna Guidetti، نويسنده , , Krista Haanstra، نويسنده , , Margaret Jonker، نويسنده , , Loredana Cleris، نويسنده , , Michele Magni، نويسنده , , Franca Formelli، نويسنده , , Alesssandro M. Gianni، نويسنده ,
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).
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.
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.