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La transfusion de concentres de granulocytes est une transfusion rare qui, malgre les avancees et l’evolution de l’arsenal therapeutique dans la prise en charge des complications infectieuses des hemopathies, garde des indications incontournables. Sa mise en œuvre implique de se plier a un certain nombre de contraintes specifiques a ce produit d’ordres reglementaire et pratique. Une mobilisation, une organisation et une coordination de tous les intervenants sont indispensables. Controversee a propos de son efficacite et de ses effets secondaires possibles, elle reste cependant parfois le seul espoir therapeutique pour le malade.

International audience; BACKGROUND: The short-term effects of granulocyte-colony-stimulating factor (G-CSF) have been extensively studied, but recent reports of G-CSF-induced genetic perturbations raised concerns regarding its long-term safety. In this respect, duration of G-CSF-induced perturbations has been less studied than short-term effects and needs to be evaluated. STUDY DESIGN AND METHODS: G-CSF mobilization-induced immunologic alterations were prospectively analyzed in a cohort of 24 healthy donors. Blood samples were taken before G-CSF administration; at the time of administration; and at 1, 3, 6, and 12 months and analyzed for blood cell counts and in vitro cytokines (interleukin [IL]-2, -8, and -10) and immunoglobulin production, quantified in the culture supernatant of peripheral blood mononuclear cells (PBMNCs) after, respectively, phytohemagglutinin and pokeweed mitogen stimulation. RESULTS: Platelet, granulocyte, monocyte, B, and dendritic blood cell counts as well as the IL-2, -8, and -10 secretion by PBMNCs, perturbed at the time of G-CSF mobilization, returned to baseline values at 1 month, with T-cell and natural killer cell counts recovering at 3 months. In vitro immunoglobulin production was increased up to 6 months after mobilization. CONCLUSION: Although assessment of the potential long-term risk of G-CSF administration will require prolonged observation of larger cohorts, our data show that the duration of immunologic perturbations may be more persistent than previously anticipated, especially for B-cell functional alterations. Most perturbations remain, however, transient with a return to baseline values within 1 year.

To the editor: Lymphocytes from granulocyte colony-stimulating factor (G-CSF)–mobilized donors display epigenetic and genetic alterations similar to those observed in leukemia patients.[1][1] To further evaluate the scope and duration of G-CSF–induced genetic alterations, 24 healthy donors were

The short-term immunological effects of granulocyte-colony stimulating factor (G-CSF) administration have been extensively studied, but concerns regarding its long-term safety have been raised by recent reports such as G-CSF-induced genetic perturbations (Nagler et al, Exp Hematol, 2004) as analyzed in a limited number of donors. In response to such concerns, we conducted a prospective study to further evaluate both short and long-term immunologic and cytogenetic alterations potentially induced by G-CSF mobilization in a cohort of 24 consecutive healthy donors. Blood samples were taken before and at time of G-CSF administration and of cytapheresis as well as 1, 3, 6 and 12 months after. G-CSF treatment followed by cytaphereris induced a significant blood platelet count decrease while granulocyte, monocyte, B as well as dendritic cell (monocyte-derived DC and even more so plasmocytoid DC) blood counts increased. Such perturbations were found to return to baseline values at one month. T-cell (both CD4 and CD8) as well as NK-cell counts decreased significantly after cytapheresis and did not recover normal values before 3 months. In vitro immunoglobulin G and M production by pokeweed mitogen-stimulated PBMC was found to be significantly (P < 10−5) increased of 63+/−7% and 84+/−7% over baseline values; increases that persisted up to 6 months after mobilization. Such an observation is in line with our previous findings pertaining to enhanced humoral immune reconstitution after allo- PBSCT (Lapierre et al, Blood 2001, Blood 2002; Tayebi et al., Br J Haematol 2001). Quite strikingly, G-CSF mobilization was also associated with significant (P < 10−6) increased PBMC aneuploidy, analyzed by in situ hybridization of chromosomes 8 and 17 centromere-specific fluorescent probes. Such increase in the frequency of aneuploïd cells was not observed in CD34+ selected cells, suggesting that G-CSF mobilization did not affect CD34+ cells with regard to cytogenetic abnormalities and that the increase in aneuploidy was induced in more mature cells. The frequency of chromosomes 8 and 17 aneuploidy increased an average of 4.5 and 4.3-fold, respectively, after G-CSF mobilization (before mobilization: 1.2+/−0.1% and 2.4+/−0.2%; after mobilization: 4.2+/− 0.4% and 8.8+/−0.4% for chromosome 8 and 17, respectively). Cells with multisomy, rare events before mobilization (recorded in 5/24 donors and at very low levels (< 0.2%)), were observed at significantly higher frequencies in all 24 donors after mobilization. On the other hand, cells with monosomy and cells with trisomy were detectable at baseline in all donors although at low frequencies which increased significantly after mobilization. The level of aneuploidy subsequently decreased after G-CSF mobilization, but, importantly remained significantly higher than baseline values at three and six months after mobilization. The frequency of cells with monosomy was higher, and returned to baseline values more gradually than the frequency of cells with trisomy or multisomy. In conclusion, our data show that immunological and cytogenetic perturbations induced by G-CSF administration in normal donors may be more pronounced and persistent than previously described. Such perturbations remain however transient with a return to baseline values within one year for most perturbations. Consequences, if any, of such alterations for the donor are presently unknown. Although EBMT and NMDP surveys have no shown any evidence in favor of an increased incidence of malignant hemopathies or solid tumors in mobilized normal donors, assessment of the potential long-term risk of G-CSF administration will require prolonged observation of large G-CSF-mobilized donor cohorts.