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

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

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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.

Original languageEnglish
Pages (from-to)68-75
Number of pages8
JournalExperimental Hematology
Volume32
Issue number1
DOIs
Publication statusPublished - Jan 2004

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Granulocyte Colony-Stimulating Factor
Primates
Cell Culture Techniques
Injections
Blood Cell Count
defibrotide
Macaca mulatta
Therapeutics
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with defibrotide and recombinant human granulocyte colony-stimulating factor. / Carlo-Stella, Carmelo; Di Nicola, Massimo; Longoni, Paolo; Milani, Raffaella; Milanesi, Marco; Guidetti, Anna; Haanstra, Krista; Jonker, Margaret; Cleris, Loredana; Magni, Michele; Formelli, Franca; Gianni, Alesssandro M.

In: Experimental Hematology, Vol. 32, No. 1, 01.2004, p. 68-75.

Research output: Contribution to journalArticle

Carlo-Stella, Carmelo ; Di Nicola, Massimo ; Longoni, Paolo ; Milani, Raffaella ; Milanesi, Marco ; Guidetti, Anna ; Haanstra, Krista ; Jonker, Margaret ; Cleris, Loredana ; Magni, Michele ; Formelli, Franca ; Gianni, Alesssandro M. / Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with defibrotide and recombinant human granulocyte colony-stimulating factor. In: Experimental Hematology. 2004 ; Vol. 32, No. 1. pp. 68-75.
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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.",
author = "Carmelo Carlo-Stella and {Di Nicola}, Massimo and Paolo Longoni and Raffaella Milani and Marco Milanesi and Anna Guidetti and Krista Haanstra and Margaret Jonker and Loredana Cleris and Michele Magni and Franca Formelli and Gianni, {Alesssandro M.}",
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T1 - Mobilization of primitive and committed hematopoietic progenitors in nonhuman primates treated with defibrotide and recombinant human granulocyte colony-stimulating factor

AU - Carlo-Stella, Carmelo

AU - Di Nicola, Massimo

AU - Longoni, Paolo

AU - Milani, Raffaella

AU - Milanesi, Marco

AU - Guidetti, Anna

AU - Haanstra, Krista

AU - Jonker, Margaret

AU - Cleris, Loredana

AU - Magni, Michele

AU - Formelli, Franca

AU - Gianni, Alesssandro M.

PY - 2004/1

Y1 - 2004/1

N2 - 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.

AB - 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.

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