References of "BARON, Frédéric"
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See detailInfusion of CliniMACS (Myltenyi Biotec) Enriched Regulatory T Cells Delays Experimental Xenogeneic Graft-versus-Host Disease
Hannon, Muriel ULg; Lechanteur, C.; Somja, Joan ULg et al

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 15

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See detailThe Immunomodulating Peptide Thymosin Alpha 1 Has no Effect on Multiple Myeloma Evolution and on Immune Reconstitution
Binsfeld, Marilène ULg; Otjacques, Eléonore ULg; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 41

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See detailKinetics of IL-7 and IL-15 Levels after Allogeneic Peripheral Blood Stem Cell Transplantation following Nonmyeloablative Conditioning
De Bock, Muriel; Fillet, Marianne ULg; Hannon, Muriel ULg et al

in PLoS ONE (2013), 8(2), 55876

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were ... [more ▼]

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were obtained before conditioning and about once per week after transplantation until day 100. Samples were aliquoted and stored at 280uC within 3 hours after collection until measurement of cytokines. IL-7 and IL-15 levels were measured by ELISAs. Results: Median IL-7 plasma levels remained below 6 pg/L throughout the first 100 days, although IL-7 plasma levels were significantly higher on days 7 (5.1 pg/mL, P = 0.002), 14 (5.2 pg/mL, P,0.001), and 28 (5.1 pg/mL, P = 0.03) (but not thereafter) than before transplantation (median value of 3.8 pg/mL). Median IL-15 serum levels were significantly higher on days 7 (12.5 pg/mL, P,0.001), 14 (10.5 pg/mL, P,0.001), and 28 (6.2 pg/mL, P,0.001) than before transplantation (median value of 2.4 pg/mL). Importantly, IL-7 and IL-15 levels on days 7 or 14 after transplantation did not predict grade II–IV acute GVHD. Conclusions: These data suggest that IL-7 and IL-15 levels remain relatively low after nonmyeloablative transplantation, and that IL-7 and IL-15 levels early after nonmyeloablative transplantation do not predict for acute GVHD. [less ▲]

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See detailAllogreffe de cellules souches hématopoïétiques chez le patient âgé : jusqu'à quel âge ?
SERVAIS, Sophie ULg; WILLEMS, Evelyne ULg; Beguin, Yves ULg et al

in Revue Médicale de Liège (2013), 68(1), 38-43

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic ... [more ▼]

In the last decades, the upper age limit for allogeneic hematopoietic cell transplantation has increased from 50-60 years to 70-75 years of age, in part due to the development of allogeneic transplantation following reducedintensity or truly nonmyeloablative conditioning. This review describes challenges and opportunities of allogeneic hematopoietic cell transplantation in the elderly. [less ▲]

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See detailNeutrophil Extracellular Traps (NET) Entrap and Kill Borrelia burgdorferi sensu stricto Spirochetes and Are not Affected by Ixodes ricinus Tick Saliva.
MENTEN-DEDOYART, Catherine ULg; Faccinetto, Céline; Golovchenko, Maryna et al

in Journal of Immunology (2012), 189(11), 5393-5401

Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). They are transmitted mainly by Ixodes ricinus ticks ... [more ▼]

Lyme disease is a pathology caused by members of the Borrelia burgdorferi sensu lato (s.l.) complex, most often by B. burgdorferi sensu stricto (s.s.). They are transmitted mainly by Ixodes ricinus ticks. After a few hours of infestation, neutrophils massively infiltrate the bite site. They can kill Borrelia via phagocytosis, oxidative burst and hydrolytic enzymes. However, factors in tick saliva promote propagation of the bacteria in the host even in the presence of a large number of neutrophils. Neutrophil extracellular trap (NET) consists in the extrusion of the neutrophil’s own DNA, forming traps that can retain and kill bacteria. The production of reactive oxygen species (ROS) is apparently associated with the onset of NEtosis. Here we describe NETs formation at the tick bite site in vivo in mice. We show that Borrelia burgdorferi s.s. spirochetes become trapped and killed by NETs in humans and that the bacteria do not seem to release significant nucleases to evade this process. Saliva from I. ricinus did not affect NET formation by human neutrophiles or it stability. However, it strongly decreased neutrophil ROS production, suggesting that a strong decrease of hydrogen peroxide does not affect NET formation. Finally, round bodies were observed trapped in NETs, some of them staining as live cells. This observation could help contribute to a better explanation of erythema migrans. [less ▲]

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See detailImpact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia : a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
Baron, Frédéric ULg; Labopin, M.; Niederwieser, D. et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2012), 26(12), 2462-2468

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced ... [more ▼]

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)¼0.7, P¼0.02) translating into a trend for better overall survival (OS; HR¼1.3; P¼0.07). Grade II acute GVHD had no net impact on OS, while grade III–IV acute GVHD was associated with a worse OS (HR¼0.4, Po0.0.001) owing to high risk of nonrelapse mortality (NRM; HR¼5.2, Po0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR¼0.72; P¼0.07) translating into a better OS (HR¼1.8; Po0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR¼0.65; P¼0.02) but also with higher NRM (HR¼3.5; Po0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (Po0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR¼0.65; P¼0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. [less ▲]

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See detailRapamycin Prevents Experimental Sclerodermatous Chronic Graft-versus-Host Disease in mice
Belle, Ludovic ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 14

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See detailWhat is the Contribution of Host-Derived CMV Immunity after Allogeneic Transplantation following Non-Myeloablative Conditioning?
MENTEN, Catherine ULg; Castermans, E.; Hannon, Muriel ULg et al

in Haematologica (2012), 97(Supplement 1), 720

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See detailEvidence for Expansion of Host-derived CMV-specific CD8+ T cells after Allogeneic Transplantation with Non-Myeloablative Conditioning
MENTEN, Catherine ULg; Castermans, E.; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 16

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See detailRapamycin prevents experimental sclerodermatous chronic graft-versus-host disease in mice
Belle, Ludovic ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

Conference (2012)

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that ... [more ▼]

Background: The most widely used mice model of chronic graft-versus-host disease (cGvHD) is an MHC-matched bone marrow transplantation model of sclerodermatous cGvHD. A limitation of that model is that mortality is relatively low, making difficult to study the impact of potentially therapeutic compounds. Aims: To develop a more severe model of cGVHD and to assess the impact of Rapamycin administration in that model. Results: Lethally irradiated Balb/C mice were injected with 10x106 bone marrow cells and 70x106 splenocytes from B10.D2 donor mice. Twenty-one days later, all mice developed cGvHD. For the severe model, donor B10.D2 mice were injected with 0.5x106 splenocytes from Balb/C twenty-one days before transplantation. All mice from the severe model (n=8) died a median of 32 days while 3 of 7 mice in the classical model survived beyond day 52. Mean survival was decreased in the severe model compared to the classical model (32 days versus 37 days; p=0.0185). Recipient mice in the severe group experienced higher weight loss, hair loss and skin fi brosis. Numbers of T lymphocytes (231.9 ± 151.4 versus 951 ± 532.8; p=0.0032) and CD4+ T cells (63.25 ± 41.93 versus 135.0 ± 14.39; p=0.0018) per microliter of blood at day 21 were lower in the severe group than in the classical model. Moreover, number of regulatory T cells (Tregs) was decreased in the severe model (1.250 ± 0.8864 versus 8.000 ± 6.753; p=0.0151). We then investigated whether rapamycin administration could prevent GVHD in the severe model. All (n=8) mice treated with PBS (placebo) died a median of 32 days after transplantation, while 6 of 8 mice given 1 mg/kg/day i.p. rapamycin survived beyond day 52 (p=0.0012). Number of Tregs/μl was higher at day 21 in rapamycin-treated mice than in mice given PBS (2.000±1.195 versus 1.250±0.8864; p=0.0796). Moreover, number of naïve CD4+T (10.00±4.192 versus 30.25±5.185; p= 0.0089) and effector memory T cells (EMT) (30.67±3.180 versus 67.33±7.881; p= 0.0125) were higher in rapamycin mice. Finally, proliferation of EMT (assessed by fl ow cytometry using Ki-67) was higher in PBS than in rapamycin mice (45.28%±4.084 versus 31.90%± 2.003; p=0.0474). Conclusion: We have developed a mice model of severe cGVHD. Interestingly, rapamycin prevented death from cGVHD in that model, perhaps through in vivo expansion of Treg. [less ▲]

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See detailValue of infliximab (Remicade) in patients with low-risk myelodysplastic syndrome. Final results of a randomized phase II trial (EORTC trial 06023) of the EORTC Leukemia Group
Baron, Frédéric ULg; Suciu, Stefan; Amadori, Sergio et al

in Haematologica (2012), 97(4), 529533

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade) is an anti-tumor-necrosis factor alpha chimeric ... [more ▼]

Tumor-necrosis factor alpha activity has been correlated to ineffective erythropoiesis in lower risk myelodysplastic syndromes. Infliximab (Remicade) is an anti-tumor-necrosis factor alpha chimeric antibody that is used in the treatment of patients with heumatoid arthritis or Crohn's disease. Forty-six patients with myelodysplastic syndromes and a relatively low risk of developing acute leukemia were included in a randomized phase II study assessing the therapeutic activity of two dosages of infliximab administration (3 mg/kg versus 5 mg/kg). The primary endpoint was the response rate. Responses were observed in 3 of 22 patients (13.1%) randomized to the 3 mg/kg arm, versus 0 of 21 patients randomized in the 5 mg/kg arm. According to the statistical design of the current study, neither of the two infliximab dose schedules tested showed sufficient activity as a single agent in this cohort of unselected patients with early myelodysplastic syndrome. [less ▲]

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See detailBone marrow-derived mesenchymal stromal cells failed to prevent experimental xenogeneic graft-versus-host disease
Bruck, France; de Leval, Laurence; Belle, Ludovic ULg et al

Poster (2012)

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See detailImatinib and Nilotinib Inhibit Hematopoietic Progenitor Cell Growth, but Do Not Prevent Adhesion, Migration and Engraftment of Human Cord Blood CD34+ Cells
Belle, Ludovic ULg; Bruck, France; FOGUENNE, Jacques ULg et al

in PLoS ONE (2012), 7(12), 52564

Background: The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to ... [more ▼]

Background: The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34+ cells. Design and Methods: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rc (null) mice. <br />Results: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34+ cell cycle entry. Adhesion of CD34+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1a gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. <br />Conclusions: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe. [less ▲]

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See detailComparison of Immune Reconstitution after Hematopoietic Stem Cell Transplantation with Flu-TBI versus TLI-ATG Conditioning
Hannon, Muriel ULg; Humblet-Baron, S.; Graux, C. et al

in Haematologica (2012), 97(Supplement 1), 180

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See detailAdaptation of a Murine Chronic GVH Model to Study Graft versus Myeloma Effect after Allogeneic Transplantation
Binsfeld, Marilène ULg; Belle, Ludovic ULg; Hannon, Muriel ULg et al

in Belgian Journal of Hematology (2012), Abstracts book(Supplement of 27th General Meeting of the Belgian Hematological Society), 16

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See detailImpact of chronic graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukaemia: A report from the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation
Baron, Frédéric ULg; Labopin, M.; Niederwieser, D. et al

Conference (2012)

We investigated the impact of occurrence of GVHD on transplantation outcomes in a large cohort of AML pts given allogeneic PBSC after RIC conditioning. Data from 1859 AML pts in fi rst (n=1439) or second ... [more ▼]

We investigated the impact of occurrence of GVHD on transplantation outcomes in a large cohort of AML pts given allogeneic PBSC after RIC conditioning. Data from 1859 AML pts in fi rst (n=1439) or second (n=420) CR transplanted between 2000 and 2009 following a RIC regimen at EBMT affi liated centres were analyzed. Pts were given PBSC from HLA-identical sibling (MRD, n=1208), or from HLA-matched unrelated donors (MUD, n=651). ATG was given in 269 (22%) MRD and in 267 (41%) MUD recipients, respectively, while 151 (13%) MRD and 165 (25%) MUD recipients received in-vivo T cell depletion with alemtuzumab. The impact of chronic GVHD (cGVHD) on outcomes was assessed using time-dependent multivariate Cox models and in a landmark analysis at 18 months after transplant. The 3-y cumulative incidence of cGVHD was 47%. Fifty-three percent of patients with cGVHD had extensive cGVHD, while the remaining 47% had limited cGVHD. In multivariate analyses, occurrence of grade II-IV aGVHD was associated with a lower risk of relapse (HR=0.8; P=0.04), a higher risk of chronic (HR=2.2; P<0.001) and extensive chronic GVHD (HR=2.8; P<0.001), a higher risk of NRM (HR=2.4 P<0.001), a worsened LFS (HR=1.3; P=0.01), and a worsened OS (HR=1.5; P<0.001). In multivariate time-dependent analyses, occurrence of limited cGVHD was associated with a lower risk of relapse (HR=0.7; P=0.05), comparable NRM (HR=1.4; P=0.16), comparable LFS (HR=0.9; P=0.29) and better OS (HR=0.5; P<0.001), while occurrence of extensive cGVHD was associated with a lower risk of relapse (HR=0.6; P=0.01), higher NRM (HR=3.2; P<0.001), a trend for worsened LFS (HR=1.3; P=0.06) and comparable OS (HR=0.9; P=0.34). In a landmark analysis in patients who were leukemia-free at 18 months after transplantation (n=776), 2-year relapse, NRM, LFS and OS were 16±2%, 2.5±1%, 82±2%, and 89±2%, respectively, in patients without cGVHD before the landmark time-point, versus 9±1% (P=0.001), 8±1% (P<0.001), 83±2% (P=0.65), and 86±2% (P=0.38), respectively, in patients with cGVHD before the landmark time-point. In conclusion, in this cohort of AML patients transplanted in remission, occurrence of cGVHD was associated with a lower risk of relapse that translated to better OS in patients with limited cGVHD but not in those with extensive cGVHD who experienced higher long term NRM. These results highlight the role of the GVT effect in RIC allo-SCT, but also the need for improving the prevention of severe cGVHD in pts receiving RIC allo-SCT. [less ▲]

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See detailImpact of alemtuzumab versus anti-thymocyte globulin after unrelated allogeneic stem cell transplantation with reduced-intensity conditioning as treatment for AML in CR1: a survey from the Acute Leukaemia Working Party of the EBMT
Baron, Frédéric ULg; Labopin, M.; Mufti, G. et al

Conference (2012)

In vivo T cell depletion of the graft with anti-thymocyte globulin (ATG) or with alemtuzumab has been frequently used in the setting of RIC allo-SCT from unrelated donors. This survey compared allo-SCT ... [more ▼]

In vivo T cell depletion of the graft with anti-thymocyte globulin (ATG) or with alemtuzumab has been frequently used in the setting of RIC allo-SCT from unrelated donors. This survey compared allo-SCT outcomes between 364 AML patients in first CR given unrelated PBSC after chemotherapy-based RIC and given either ATG (n=213) or alemtuzumab (n=151) in the conditioning regimen. Alemtuzumab patients were more frequently given grafts from HLA-mismatched donors (30% versus 16% having at least 1/10 HLA-mismatch with their donor, P=0.005), and were conditioned more often with melphalan-based RIC (62%), while ATG recipients were more frequently conditioned with busulfan-based RIC (84%). Median time to neutrophil engraftment (>500 ANC) was 16 days in ATG recipients, versus 12 days in alemtuzumab recipients (P<0.001). The incidence of grade II-IV acute GVHD was 28% in ATG recipients (9 patients with grade IV) and 24% (NS) in alemtuzumab recipients (2 patients with grade IV). Two-year incidences of chronic GVHD, relapse and NRM were 45%, 23% and 14%, respectively, in ATG recipients, and 47% (NS), 25% (NS) and 25% (P=0.008), respectively, in alemtuzumab recipients. Two-year OS and LFS were 69% and 63%, respectively, in ATG recipients, versus 55% (P=0.003) and 51% (P=0.02), respectively, in alemtuzumab recipients. Death from infection occurred in 7% of ATG recipients, versus 12% of alemtuzumab recipients. When the analysis was restricted to the 210 patients given grafts from 10/10 HLA-matched unrelated donors, the use of alemtuzumab (n=64) remained signifi cantly associated with higher NRM (22% vs 9%, P=0.007), lower LFS (58% vs 69%, P=0.07), and lower OS (62% vs 74%, P=0.04). In multivariate analyses (performed in patients given grafts from 10/10 HLA-matched donors), in comparison to the use of ATG, the use of alemtuzumab was associated with higher NRM (HR=2.5, P=0.025), a statistically non-signifi cant but higher relapse rate (HR=1.7, P=0.18), and signifi cantly worse LFS (HR=0.5, P=0.013) and OS (HR=0.4, P=0.002). In summary, this homogeneous cohort of AML patients transplanted in fi rst CR and given PBSC grafts from unrelated donors, the use of alemtuzumab in comparison with ATG was associated with worse LFS and OS. [less ▲]

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