Publications (76)281.01 Total impact
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Article: CD34+ cells and CD34+CD38- subset from mobilized blood show different patterns of adhesion molecules compared to those from steady-state blood, bone marrow, and cord blood.
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ABSTRACT: As suggested previously, a down-regulation of some cellular adhesion molecules (CAMs) on CD34(+) hematopoietic progenitor cells (HPC) may contribute to their egress from bone marrow (BM) to peripheral blood (PB) by decreasing their adhesion to BM stromal cells. Besides counting the percentage of CAM-positive cells, we decided to define clearly the antigen density (AgD) of the CAM on mobilized- and steady-state CD34(+) HPC using QIFIKIT calibration beads. Five sources of cells were compared: PB and BM from normal donors (nPB, nBM) cord blood (CB), mobilized PB obtained from leukapheresis products (LKP), and mobilized BM (mBM) samples. In our study the CAM-AgD was the lowest on CD34(+) cells in LKP which, on the contrary, contained the highest percentage of CD117(+), CD54(+), CD58(+) cell subsets. As for CB, a greater proportion of CD44(+) and CD62L(+) cells was observed in LKP than in other products. The LKP-CD34(+) cell population contained a greater percentage of CD11a(+) cells when compared to mBM, but the lowest percentage of CD49d(+) and CD49e(+) cells when compared to all products. The proportion of the CD34(+)CD38(-) immature subset expressing CD11a, CD44, CD54, or CD62L was greater in LKP than in mBM; the CD62L-AgD was higher in LKP than in mBM. This quantitative analysis clearly showed a downregulation of all CAM on LKP-CD34(+). The CD44, CD62L, CD11a, and CD54 AgD decrease appears to be specifically involved in the egress of the CD34(+) subsets into PB. The control of antigen density of these adhesion molecules is likely to be clinically important for effective mobilization of HPC as well as for rapid engraftment following HPC transplant.Journal of Hematotherapy & Stem Cell Research 11/2003; 12(5):473-89. -
Article: Lack of involvement of the Fas system in ankylosing spondylitis.
Annals of the Rheumatic Diseases 08/2000; 59(7):574. · 8.73 Impact Factor -
Article: Cost-effectiveness of CD34+ dose in peripheral blood progenitor cell transplantation for non-Hodgkin's lymphoma patients: a single centre study.
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ABSTRACT: Intensive high-dose chemotherapy with peripheral blood progenitor cell (PBPC) transplantation is a common strategy for aggressive non-Hodgkin's lymphomas (NHL). A retrospective cost-effectiveness analysis of CD34+ cell dose was carried out. Between 1994 and 1998, 28 patients were included. Efficacy was measured by the length of aplasia. Data collection concerned the period from graft day until discharge from hospital, and the post-graft period until graft day +100. Patients transplanted using a cell dose greater than 5 x 106/kg were found to have a faster hematological recovery. Average length of post-graft hospitalization was shorter and fewer blood products were required for patients with more than 5 x 106/kg CD34+ cells transplanted. Hospitalization was the major cost driver. A large reduction in procedure cost was obtained with a CD34+ cell count higher than 5 x 106/kg (-US$2740, -11%). This difference was directly related to hospitalization (-US$860) and platelet units transfused (-US$1,340). A sensitivity analysis showed the robustness of results. Our findings indicated that a CD34+ cell dose higher than 5 x 106/kg was more cost-effective than a lower dose in NHL patients. The collection of 5 x 106/kg CD34+ cells appeared necessary to optimize the PBPC procedure.Bone Marrow Transplantation 06/2000; 25(9):997-1002. · 3.75 Impact Factor -
Article: Low dose T-cell lymphocyte infusion combined with marrow T-cell depletion as prophylaxis of acute graft vs host disease for HLA identical sibling bone marrow transplantation.
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ABSTRACT: T-cell depletion (TCD) of the bone marrow graft remains the most effective method to prevent severe graft versus host disease after allogeneic bone marrow transplantation. Early studies of HLA-identical sibling transplants showed that although T-cell depletion decreased GVHD, T-cell depleted transplants had higher risks of graft failure and leukemia relapse, leukemia free survival (LFS) was not improved compared to non-T-cell depleted transplants. In order to avoid graft failure and increased risk of relapse associated with this approach, we initiated a pilot study of T-cell depletion of the marrow graft combined with reinfusion of a fixed quantity of CD2+ peripheral blood T-cells. Depletion technique consisted in negative purging using CD2 and CD7 monoclonal antibodies (MoAbs) followed by rabbit complement cytolysis. This approach was associated with an intensified conditioning regimen using total body irradiation, high-dose cytosine arabinoside and melphalan (TAM) for all but one patient. Twenty-one patients were included with a mean age of 40 years. Only one acute severe Graft Versus Host Disease (GVHD) was observed and all patients engrafted. At 63 months, probability of survival is 42.86% with a relapse risk of 19.89%, two patients died from B-cell lymphoproliferative disease, seven other died from the procedure partially because of the use of the TAM as pretransplant regimen. This approach is being pursued by a gene therapy trial using herpes-simplex - 1 thymidine kinase gene expressing peripheral donor T-cells.Hematology and Cell Therapy 05/1999; 41(2):31-7. -
Article: Interferon gamma, IL2, IL4, IL10 and TNFalpha secretions in multiple sclerosis patients treated with an anti-CD4 monoclonal antibody.
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ABSTRACT: In order to better understand the mechanisms of action of a monoclonal anti-CD4/BF5 antibody(mAb), cytokine secretions were studied in 14 multiple sclerosis (MS) patients treated in a phase 1 trial. Secretion patterns of IFNgamma, IL2, IL4, IL10 and TNFalpha by peripheral blood mononuclear cells were studied before (DO) and after (D30) the treatment. We decided to undertake this study because in a previous one we observed no variations in serum levels of TNFalpha, IFNgamma, IL1, IL6. Results showed significant reductions in IFNgamma, IL2 and TNFalpha secretions after treatment. The anti-CD4 mAb seemed to act on both Th1- and Th2-cells but with preferential action on Th1-cells. Results on Th2-cells were less obvious even though a significant decrease in IL10 was observed. There was no correlation between any of the immunological markers studied and disease activity. This study demonstrates that pharmacological modifications of the CD4 receptor can induce variations in several cytokine secretion levels. It also stresses the role played by Th1- and Th2-cells in the etiopathogenesis of MS.Autoimmunity 02/1999; 29(2):87-92. · 2.47 Impact Factor -
Article: T-cell immune defect and B-cell activation in renal transplant recipients with monoclonal gammopathies.
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ABSTRACT: Monoclonal immunoglobulins (molg) have repeatedly been described in organ and bone marrow transplantation. Although their exact significance is not known, their occurrence is often associated with intensive immunosuppression. We investigated whether molg reflect T-cell immune defect and B-cell activation in renal transplant recipients. Immunofixations and lymphocyte subset analysis (CD4, CD8, CD19) were performed in 182 renal transplant recipients. Soluble CD23 concentrations were measured in patients with molg and in control transplant patients without molg. Monoclonal immunoglobulins were identified in 54 patients (29.6 %). Transplant endurance was shorter (62 +/- 53 months vs 81 +/- 47 months; P < 0.02) and age was older (53 +/- 13 years vs 46 +/- 13 years; P < 0.005) in patients with molg. Maintenance immunosuppression did not differ between patients with and without molg. Mean CD4-cell count was significantly lower in patients with molg (387 +/- 286/mm(3) vs 538 +/- 341/mm(3); P < 0.005). Both CD8- and CD19-cell counts were similar for the 2 groups. Soluble CD23 concentrations were higher in patients with abnormal immunoglobulin values than in patients with normal immunofixation (12.8 +/- 8 vs 1.9 +/- 1.8 microg/l; P < 0. 005). Our study provides new evidence that molg reflect T-cell immune defect in renal transplant recipients. Further studies are required to determine whether CD4-cell count and sCD23 may help to predict the risk of lymphoma in transplant patients with molg.Transplant International 01/1999; 12(4):250-3. · 2.92 Impact Factor -
Article: Comparative analysis of class I, II and III epitope-detecting CD34 monoclonal antibodies by quantitative flow cytometry.
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ABSTRACT: The aim of this study was to compare different CD34 monoclonal antibodies (MAbs) belonging to three different classes: MY10 class I, QBend10 class II, a mixture of three selected MAbs class I and II designated as CD34 Pool, and 8G12 class III. Bone marrow (BM) samples from 13 healthy donors were analyzed for: 1) percentage of CD34+ cells, 2) quantitative expression of CD34 epitopes (antigen's density - AgD) using a quantitative indirect immunofluorescence (QIFI) test, 3) study of CD34+ cell subsets defined by CD34 and CD38 coexpression. 8G12 MAb showed the highest reactivity with regard to the percentage of detected CD34+ cells and AgD on these cells. A nearly identical percentage of CD34+ cells was detected with CD34 Pool, but with a lower AgD. With QBend10, the percentage of CD34 expressing cells was insignificantly decreased and the AgD was slightly lower. The expression of the MY10 epitope was the lowest and was detected on the lowest number of CD34+ cells. Concerning CD34 and CD38 coexpressing subset, we observed that 8G12 class III MAb detected CD34loCD38dim cells with comparable efficiency with MY10 class I MAb, but with significantly higher level than QBend10 class II and CD34 Pool class I+II MAbs. The CD34hiCD38dim subset was detected with the same efficiency by QBend10, CD34 Pool or 8G12 MAbs but with significantly higher frequency than MY10 MAb. In conclusion: class II and III MAbs appear preferable for flow cytometric quantification of CD34+ cells; for CD34+ cell subsets determination class III MAbs should be suitable.Hematology and Cell Therapy 01/1999; 40(6):259-68. -
Article: In vitro study of alloreactivity and microchimerism after injection of dendritic cells and anti-CD4 monoclonal antibody in a combination of Lewis-Wistar Furth rats: preliminary data.
Transplantation Proceedings 10/1998; 30(6):2857-8. · 1.00 Impact Factor -
Article: CD4 lymphocytopenia in long-term renal transplant recipients.
Transplantation Proceedings 10/1998; 30(6):2859-60. · 1.00 Impact Factor -
Article: A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.
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ABSTRACT: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo. Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated. The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant. No significant improvement in RA after murine anti-CD4 Mab was observed.The Journal of Rheumatology 08/1998; 25(8):1457-61. · 3.69 Impact Factor -
Article: Soluble intercellular adhesion molecule 1 in spondylarthropathies.
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ABSTRACT: The aim of the study was to evaluate the soluble form of intercellular adhesion molecule 1 (sICAM-1), a ligand of LFA-1, in the serum of patients with spondylarthropathies (SpA) and to look for a correlation with several inflammatory parameters. sICAM-1 levels were measured by ELISA in 25 SpA patients, 20 healthy controls and 20 patients with rheumatoid arthritis (RA). Results showed that sICAM-1 levels were increased (but not significantly) in SpA patients compared with controls; high levels (> 400 ng/ml) where found in 28% of SpA patients but in none of the RA or control groups. In SpA, correlations were found between sICAM-1 and erythrocyte sedimentation rate, C-reactive protein and interleukin 6, but not with tumour necrosis factor alapha or IgA. These correlations were absent in RA. In conclusion, these results suggest that sICAM-1 levels in SpA may reflect the acute phase of inflammation.Clinical Rheumatology 02/1998; 17(3):202-4. · 2.00 Impact Factor -
Article: Nasal mucosa inflammation induced by oxygen administration in humans.
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ABSTRACT: The effect of oxygen toxicity in human airways is still poorly documented. We prospectively evaluated the inflammatory reaction induced by nasal oxygen exposure in an experimental setting. Healthy subjects without nasal symptoms were exposed to high FIO2 during 5 h. Oxygen was delivered from a tank at a flow of 4 l/min to one nostril of each subject and both nostrils were studied. Mucociliary clearance was measured as saccharine nasal transit time (SNTT). Nasal lavage was performed with 5 ml normal saline and the fluid recovered was processed for cytology and measurements of cytokines concentrations: TNF alpha, IL-6, IL-8 and soluble ICAM-1. Under local anaesthesia, biopsies were performed for immunochemistry and electron microscopy. After oxygen exposure mucociliary clearance decreased and SNTT increased from 16 [9-21] to 20.5 [14-32] min (median and extremes; P < 0.1). In the lavage fluid, concentration of IL-6 was higher in the oxygen-exposed nostril (40.5 [11-128] pg/ml) than in the non-exposed one (7 [0-34] pg/ml; P < 0.05). There was also a trend for a higher IL-8 in the exposed than in the non-exposed nostril, (respectively 501 [214-587] pg/ml and 214 [122-616] pg/ml, P < 0.08), and for a higher number of polymorphonuclear cells in exposed nostril. In the mucosal biopsies substance P was not found, but ICAM-1 expression was higher in the mucosa and submucosa of the exposed nostrils where mast cells were also more abundant and showed piecemeal degranulation. In summary, we found clinical, functional and biological evidence of ongoing nasal inflammation following high FIO2 inhalation for 5 h. Since the histology and behaviour of nasal and bronchi mucosa are very similar, the same inflammatory events are likely to be occurring in the bronchi upon high concentrations of inhaled oxygen.Acta Anaesthesiologica Scandinavica 09/1997; 41(8):1011-6. · 2.19 Impact Factor -
Article: Comparison of T cell depletion strategies from bone marrow, umbilical cord and peripheral blood using five separation systems.
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ABSTRACT: The development of bone marrow transplantation in mismatched or matched unrelated donor situations, the recent use of peripheral blood stem cells for allogeneic transplants, the standardization and respect of good methodology practices highlight the need to evaluate new safe methods of T cell depletion (TCD). We have performed 79 in vitro TCD using five techniques: rabbit complement cytotoxicity, CD2-CD7 immunomagnetic depletion, CD5-CD8 panning system, CD34 positive purging and counterflow centrifugation elutriation (CCE). We analyzed these different approaches with regard to the degree of T and B depletion, recovery of progenitors and NK cells. In our hands, the 5 systems evaluated showed a TCD of between 1.3 and 3 log. The CCE, immunomagnetic, complement and panning methods all give similar a TCD of around 2 log. In contrast, we obtained a TCD of approximately 3 log with CD34 positive purging. The progenitor yield was around 50% regardless of the technique used. However, the degree of B and NK cell depletion was dependent on the method: specific TCD resulted in low BCD (under 0.5 log), whereas CCE or CD34 positive purging gave a BCD of greater than 1 log. Moreover, CD34 positive selection resulted in a virtually complete elimination of NK cells. CCE was the only technique allowing isolation of the small lymphocyte population which can be useful for adoptive therapy. To obtain TCD over three logarithms, double purging techniques are necessary. Because specific roles of T cells subsets in engraftment, graft versus host disease, Epstein Barr virus associated B cell lymphoproliferative disorders and disease relapse have not yet been completely elucidated, new techniques such as CD34 positive purging and double purging methods (positive and negative purging) need to be clinically evaluated, especially with respect to peripheral blood stem cells.Hematology and Cell Therapy 05/1997; 39(2):67-73. -
Article: Use of donor T-lymphocytes expressing herpes-simplex thymidine kinase in allogeneic bone marrow transplantation: a phase I-II study.
Human Gene Therapy 04/1997; 8(5):615-24. · 4.22 Impact Factor -
Article: Combination therapy of anti-CD4 and anti-IL6 monoclonal antibodies in a case of severe spondylarthropathy.
British journal of rheumatology 01/1997; 35(12):1330. -
Article: Comparative preclinical study of three bone marrow purging methods using PCR evaluation of residual t(14;18) lymphoma cells.
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ABSTRACT: The t(14;18) chromosomal translocation occurring in most follicular lymphomas can be exploited by a Bcl2/JH polymerase chain reaction (PCR) to detect residual disease and to monitor the effectiveness of ex-vivo tumor cell immunological purging. We first demonstrated the 10(-5) Bcl2/JH PCR sensitivity with serial dilutions of OCY-LY8 lymphoma cell lines in normal mononuclear cells; and then the specificity and reproductibility of this technique by analysing follicular and non follicular lymphoma samples. With the Bcl2/JH PCR, we tested the efficiency of three marrow purging protocols with an experimentally contaminated bone marrow either treated by three anti-B cell monoclonal antibodies (mAb) followed by three rounds of rabbit complement or two rounds of immunomagnetics beads. Samples obtained after each purging were amplified by Bcl2/JH PCR and hybridized with PFL3 probe. We were able to produce a 2 to 3 log tumor cell reduction after three rounds of complement and a 4 to 5 log reduction after two rounds of beads. This study showed that it is feasible to use the Bcl2/JH PCR technique for residual cell lymphoma detection in patients undergoing intensive chemotherapy or BM transplantation. These results indicate that ex-vivo immunomagnetic BM purging is probably superior to complement mediated lysis for the eradication of B lymphoma cells from the marrow of patients undergoing autologous transplantation.Leukemia and Lymphoma 11/1996; 23(3-4):313-21. · 2.58 Impact Factor -
Article: Biological assessment and MRI monitoring of the therapeutic efficacy of a monoclonal anti-T CD4 antibody in multiple sclerosis patients.
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ABSTRACT: An initial group of 21 patients plus a second group of 14 patients with active multiple sclerosis (MS) (18 progressive and 17 relapsing-remitting forms) were treated with a murine monoclonal anti-T CD4/BF5 antibody as part of a phase I open trial. Tolerance was relatively good: minor general side-effects occurred in 22 patients only upon the first mAb infusion. One year later, functional disability was stabilised in only six of the 35 patients and after 2 years in two patients only (among 21). One year after treatment, nine of the 17 relapsing-remitting patients were relapse-free. CD4 counts decreased dramatically 2 h after treatment. These counts were back to baseline counts at 3 months. A transient increase was found in IL-6 and TNF alpha levels 2 h after treatment, which probably accounts for the observed side effects. Cell adhesion molecule levels were not modified. Serial MRI scans were performed in the second group of 14 patients. In all of these patients, lesion modifications were observed in the three scans performed prior to treatment. Yet, no changes in the lesions were noted on the MRI scans performed over the following 3 months. These findings demonstrate the feasibility of this treatment insofar as it induced a marked CD4 lymphocyte depletion. However, it did not seem to stabilise the evolution of the disease--although one must be careful in drawing such conclusions in a phase I trial--or to curb the evolution of MRI-documented lesions.Multiple Sclerosis 03/1996; 1(4):207-12. · 4.26 Impact Factor -
Article: Clinical and immunological follow-up of patients with AIDS-associated Kaposi's sarcoma treated with an anti-IL-6 monoclonal antibody.
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ABSTRACT: Ten AIDS patients with Kaposi's sarcoma (four in stage II A, four in stage III A, one in stage III B and one in stage IV of the disease) were treated for 14 days with B-E8, an anti-IL-6 monoclonal antibody (IgG1), at a daily dose of 10 mg. No side-effects were observed, but no patients experienced a complete or partial response. No modification was noted in the analysis of lymphocyte subsets, except for a transient decline in the number of cells expressing CD56, accompanied by altered NK activity in four of the seven evaluable patients. Anti-IL-6 mAb prevented the binding of IL-6 to its cell membrane receptor, as documented by the decline in C reactive protein levels. However, anti-IL-6 mAb induced the circulation of significant amounts of IL-6, probably in the form of monomeric immune complexes. The sera, analysed on B9 cell line, demonstrated a stimulating activity, indicating that hypersensitive cells were able to cleave these complexes. This observation, together with the clinical inefficacy of the treatment, should prompt us to be careful with the use of unmanipulated single monoclonal antibodies, especially in cancer patients.Cytokines and molecular therapy 07/1995; 1(2):133-8. -
Article: Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients.
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ABSTRACT: We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)Bone Marrow Transplantation 06/1995; 15(5):669-77. · 3.75 Impact Factor -
Article: Outcome of lymphocyte subsets and cytokines during combined CD4/anti-IL-2R monoclonal antibody therapy in kidney transplantation.
Transplantation Proceedings 05/1995; 27(2):1672-3. · 1.00 Impact Factor
Top Journals
Institutions
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1989–1999
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Centre Hospitalier Régional et Universitaire de Besançon
Besançon, Franche-Comte, France
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1998
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Université de Bourgogne
Dijon, Bourgogne, France
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1995
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Centre Hospitalier Universitaire de Dijon
Dijon, Bourgogne, France
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1989–1995
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Centre de transfusion sanguine des armées (CTSA)
Clamart, Ile-de-France, France
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1991–1992
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CHRU de Strasbourg
Strasbourg, Alsace, France
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