References of "Baron, Frédéric"
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See detailThinking out of the box - New approaches to controlling GVHD
Baron, Frédéric ULg; Humblet-Baron, Stéphanie; Ehx, Grégory ULg et al

in Current Hematologic Malignancy Reports (in press)

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD ... [more ▼]

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2. [less ▲]

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See detailEffect of post remission therapy prior to reduced intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission
Warlick, Erica; Paulson, Kristjan; Brazauskas, Ruta et al

in Biology of Blood & Marrow Transplantation (in press)

The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with ... [more ▼]

The impact of pre transplant (HCT) cytarabine consolidation therapy on post HCT outcomes has yet to be evaluated after reduced intensity or non-myeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia (AML) in first complete remission (CR1) reported to the CIBMTR who received a RIC or NMA HCT from an HLA-identical sibling, HLA-matched unrelated donor (URD), or umbilical cord blood (UCB) donor in 2000-2010. We compared transplant outcomes based on exposure to cytarabine post remission consolidation. Three year survival rates were 36% (29-43%, 95% CI) in the no consolidation arm and 42% (37-47%, 95% CI) in the cytarabine consolidation arm (p=0.16). Disease free survival was 34% (27-41%, 95% CI) and 41% (35-46%, 95% CI) (p=0.15), respectively. Three year cumulative incidences of relapse were 37% (30-44%, 95% CI) and 38% (33-43%, 95% CI), respectively (p=0.80). Multivariate regression confirmed no effect of consolidation on relapse, DFS and survival. Prior to RIC/NMA HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant TRM and is reasonable if required. [less ▲]

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See detailComprehensive plasma profiling for the characterization of graft-versus-host disease biomarkers
De Bock, Muriel; BEGUIN, Yves ULg; Leprince, Pierre ULg et al

in Talanta (2014), 125

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy ... [more ▼]

Acutegraft-versus-hostdisease(aGVHD)remainsalife-threateningcomplicationofhematopoieticstem cell transplantation(HSCT)thereforelimitingitsapplication.TooptimizethemanagementofaGVHDand reduce therapy-relatedtoxicity,earlyspecific markersareneeded.Themainobjectiveofthisstudywas to uncoverdiagnosticbiomarkersbycomparingplasmaproteinprofiles ofpatientsatthetimeofacute GVHDdiagnosiswiththoseofpatientsundergoingHSCTwithoutaGVHD.Additionalanalysisofsamples taken 15daysbeforeaGVHDdiagnosiswasalsoperformedtoevaluatethepotentialofournewly discoveredbiomarkersforearlydiagnosis.Togetcomplementaryinformationfromplasmasamples, we usedthreedifferentproteomicapproaches,namely2D-DIGE,SELDI-TOF-MSand2D-LC-MSE. Weidentified andconfirmed bythemeansofindependenttechniques,thedifferentialexpression of severalproteinsindicatingsignificantly increasedinflammation responseanddisturbanceinthe coagulation cascade.Thevariationoftheseproteinswasalreadyobserved15daysbeforeGVHD diagnosis, suggestingthepotentialearlydetectionofthediseasebeforesymptomsappearance. Finally,logisticregressionanalysisdeterminedacompositebiomarkerpanelcomprising fibrinogen, fragment of fibrinogenbetachain,SAA,prothrombinfragments,apolipoproteinA1andhepcidinthat optimallydiscriminatedpatientswithandwithoutGVHD.Theareaunderthereceiveroperating characteristiccurvedistinguishingthese2groupswas0.95. [less ▲]

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See detailImpact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning all-SCT from a HLA-identical sibling donor : a report from the Acute Leukemia Working Party of the European group for Blood and Marrow Transplantation
Baron, Frédéric ULg; Labopin, M.; Blaise, D. et al

in Bone Marrow Transplantation (2014)

The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult ... [more ▼]

The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (Po0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (Po0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of o6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR¼1.1), whereas there was a suggestion for higher relapse risk in patients given X6 mg/kg ATG (HR¼1.4, P¼0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC. [less ▲]

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See detailImpact of bone marrow-derived mesenchymal stromal cells on experimental xenogeneic graft-versus-host disease
Bruck, France; Belle, Ludovic ULg; LECHANTEUR, Chantal ULg et al

in Cytotherapy (2013), 15(3), 267-279

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous ... [more ▼]

Background aims. Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation caused by donor T cells reacting against host tissues. Previous studies have suggested that mesenchymal stromal cells (MSCs) could exert potent immunosuppressive effects. Methods. The ability of human bone marrow derived MSCs to prevent xenogeneic GVHD in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice and in NOD/SCID/interleukin-2Rg(null) (NSG) mice transplanted with human peripheral blood mononuclear cells (PBMCs) was assessed. Results. Injection of 200 106 human PBMCs intraperitoneally (IP) into sub-lethally (3.0 Gy) irradiated NOD/SCID mice also given anti-asialo GM1 antibodies IP 1 day prior and 8 days after transplantation induced lethal xenogeneic GVHD in all tested mice. Co-injection of 2 106 MSCs IP on day 0 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Similarly, injection of 30 106 human PBMCs IP into sub-lethally (2.5 Gy) irradiated NSG mice induced a lethal xenogeneic GVHD in all tested mice. Injection of 3 106 MSCs IP on days 0, 7, 14 and 21 did not prevent lethal xenogeneic GVHD induced by injection of human PBMCs. Conclusions. Injection of MSCs did not prevent xenogeneic GVHD in these two humanized mice models. [less ▲]

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See detailErythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomised trial.
JASPERS, Aurélie ULg; Baron, Frédéric ULg; WILLEMS, Evelyne ULg et al

in Belgian Journal of Hematology (2013, January)

Based on the impairment of erythropoietin production after allogeneic hematopoietic cell transplantation (HCT), we previously reported in a phase-2 trial that recombinant human erythropoietin (rhEPO ... [more ▼]

Based on the impairment of erythropoietin production after allogeneic hematopoietic cell transplantation (HCT), we previously reported in a phase-2 trial that recombinant human erythropoietin (rhEPO) therapy was very efficient when started one month after transplantation. We also demonstrated that anemia after nonmyeloabalative (NM) HCT was less sensitive to rhEPO therapy than after conventional allogeneic HCT. This prompted us to confirm these findings in a prospective randomised trial. One hundred and thirty-one patients were randomised (1:1) between no treatment (arm 1) or erythropoietin (Neorecormon) at the dose of 500 U/kg/week (arm 2). Once the target Hb (13g/dL) has been attained, the dose of rhEPO was reduced by half, while it was withheld when Hb was = 14g/dL. Cohort A included 42 patients on day 28 after myeloablative HCT, cohort B 39 patients on day 28 after NMHCT, and cohort C 50 patients on day 0 of NMHCT. Primary endpoints included proportion of complete correctors (i.e. patients reaching Hb = 13g/dL) and median time to achieve Hb correction in each arm. The proportion of complete correctors before day 126 posttransplant was 0% in group 1A vs 52.4% in group 2A, 0% in group 1B vs 69.5% in group 2B and 19.1% in group 1C vs 70.2% in group 2C. Median time to achieve Hb = 13g/dL was not reached in group 1B vs 49 days in group 2B; 363 and 59 days in groups 1A and 1B respectively and 363 and 87 days in groups 3A and 3B respectively (figure 1). Hb evolution in each group is shown in figure 2. Seventyone patients (47/62 in control groups and 24/57 in treated groups, p=0.0003) required red blood cell transfusions. The difference was most pronounced in cohort B. There was no difference in rates of thrombo-embolic events or other complications between the two arms. In conclusion, this is the first trial to demonstrate that EPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. [less ▲]

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See detailLung function and airway inflammation monitoring after hematopoietic stem cell transplantation.
Moermans, Catherine ULg; Poulet, Christophe ULg; HENKET, Monique ULg et al

in Respiratory Medicine (2013), 107

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the ... [more ▼]

Background Induced sputum is a non-invasive method to investigate airway inflammation, which has been used to assess pulmonary inflammatory diseases. However, this procedure has not been studied in the context of hematopoietic stem cell transplantation (HSCT). Methods We monitored lung function in 182 patients who underwent HSCT and measured airway inflammation by sputum induction in 80 of them. We prospectively measured FEV1, FVC, DLCO, KCO, TLC, RV, exhaled nitric oxide (FeNO) as well as sputum cell counts before and 3, 6, 12, 24 and 36 months after HSCT. Results For the whole cohort there was a progressive decrease in TLC, which was significant after 3 years (p < 0.01). By contrast, there was no change in other lung functions parameters or in FeNO. Baseline sputum analysis revealed increased neutrophil counts in patients {Median (IQR): 63% (38–79)} compared to healthy subjects matched for age {Median (IQR): 49% (17–67), p < 0.001} but there was no significant change in any type of sputum cell counts over the three years. When comparing myeloablative (MA) vs non-myeloablative (NMA) conditioning, falls in FEV1, FVC and DLCO, and rise in RV and sputum neutrophils were more pronounced over the first year of observation in those receiving MA. Conclusions There was a progressive loss in lung function after HSCT, featuring a restrictive pattern. Myeloablative conditioning was associated with early rise of sputum neutrophils and greater alteration in lung function over the first year. [less ▲]

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See detailDarbepoetin-alfa and intravenous iron administration after autologous hematopoietic stem cell transplantation : A prospective multicenter randomized trial
BEGUIN, Yves ULg; Maertens, Johan; DE PRIJCK, Bernard ULg et al

in American Journal of Hematology (2013), 88

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell ... [more ▼]

We conducted a randomized study analyzing the impact of darbepoetin alfa (DA) administration with or without intravenous (i.v.) iron on erythroid recovery after autologous hematopoietic cell transplantation (HCT). Patients were randomized between no DA (Arm 1), DA 300 lg every 2 weeks starting on Day 28 after HCT (Arm 2), or DA plus i.v. iron 200 mg on Days 28, 42, and 56 (Arm 3). The proportion achieving complete hemoglobin (Hb) response within 18 weeks (primary end point) was 21% in Arm 1 (n524), 79% in Arm 2 (n525), and 100% in Arm 3 (n523; P < 0.0001). Erythropoietic response was shown to be significantly higher in Arm 3 (n546) than in Arm 2 (n550; P50.008), resulting in lower DA use, reduced drug costs, and improved quality of life scores, but the effect on transfusions was not significant. In multivariate analysis, DA administration (P< 0.0001), i.v. iron administration (P50.0010), high baseline Hb (P< 0.0001), and low baseline creatinine (P50.0458) were independently associated with faster achievement of complete Hb response. In conclusion, DA is highly effective to ensure full erythroid reconstitution after autologous HCT when started on Day 28 post-transplant. I.v. iron sucrose further improves erythroid recovery. [less ▲]

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See detailEmerging drugs for prevention of graft failure after allogeneic hematopoietic stem cell transplantation
SERVAIS, Sophie ULg; Beguin, Yves ULg; Baron, Frédéric ULg

in Expert Opinion on Emerging Drugs (2013), 18(2), 173-192

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow ... [more ▼]

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the treatment of choice for many patients suffering from hematological malignancies, severe hemoglobinopathies, bone marrow failures or severe primary immunodeficiencies. Graft rejection/failure (GF) is a life-threatening complication following allo-HSCT that is most commonly caused by the reactivity of recipient T cells, natural killer (NK) cells or antibodies against donor grafted hematopoietic cells. The increasing use of allo-HSCT following reduced-intensity conditioning (RIC) and the increasing use of alternative donors (unrelated cord blood and human leukocyte antigen (HLA)-mismatched donor) have resulted in higher frequency of GF. Areas covered: This review describes the pathogenesis and current prevention and treatment of GF as well as agents in development for GF prevention or treatment. Expert opinion: The risk of GF may be reduced in the future by optimizing the conditioning regimens and post-grafting immunosuppression, increasing the number of hematopoietic stem cells (HSCs) and/or immune cells transplanted, optimizing HSC homing and better detecting patients at high risk of GF by searching for pre-transplant donor-specific anti-HLA antibodies in patients given grafts from HLA-mismatched donors, or by closely monitoring donor T- and/or NK-cell chimerism after allo-HSCT following RIC. [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 Belgian Journal of Hematology (2013), Abstracts book(Supplement of 28th General Meeting of the Belgian Hematological Society), 38

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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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