References of "Baron, Frédéric"
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See detailErythropoietin therapy after allogeneic hematopoietic cell transplantation : a prospective randomized trial
JASPERS, Aurélie ULg; Baron, Frédéric ULg; WILLEMS, Evelyne ULg et al

in Blood (in press)

We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (n=131) were ... [more ▼]

We conducted a prospective randomized trial to assess hemoglobin (Hb) response to recombinant human erythropoietin (rhEPO) therapy after hematopoietic cell transplantation (HCT). Patients (n=131) were randomized (1:1) between no treatment (control arm) or erythropoietin (Neorecormon®) at 500 U/kg/week (EPO arm). Patients were also stratified in 3 cohorts: patients undergoing myeloablative HCT with rhEPO to start on day 28, patients given nonmyeloablative HCT (NMHCT) with rhEPO to start on day 28, and patients also given NMHCT but with rhEPO to start on day 0. The proportion of complete correctors (i.e. achieving Hb ≥ 13 g/dL) before day 126 post-transplant (primary endpoint) was 8.1% in the control arm (median not reached) and 63.1% in the EPO arm (median time 90 days) (p<0.001). Hb levels were higher and transfusions requirements decreased (p<0.001) in the EPO arm, but not during the first month in the nonmyeloablative cohort starting rhEPO on day 0. There was no difference in rates of thrombo-embolic events or other complications between the 2 arms. This is the first randomized trial to demonstrate that rhEPO therapy hastens erythroid recovery and decreases transfusion requirements when started one month after allogeneic HCT. There was no benefit to start rhEPO earlier after NMHCT. [less ▲]

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See detailImpact of co-transplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning
MOERMANS, Catherine ULg; LECHANTEUR, Chantal ULg; BAUDOUX, Etienne ULg et al

in Transplantation (in press)

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal ... [more ▼]

Background: In the context of hematopoietic stem cell transplantation (HSCT), mesenchymal stem cells (MSC) have been used to promote engraftment and prevent graft- versus-host-disease. However, in animal models, MSC were shown to cause pulmonary alterations after systemic administration. The impact of MSC infusion on lung function has not been studied in humans. The objective of the study was to investigate the impact of MSC co-infusion on lung function and airway inflammation as well as on the incidence of pulmonary infections and cytomegalovirus (CMV) reactivation after HSCT. Methods: We have prospectively followed 30 patients who underwent unrelated HSCT with MSC co-infusion after non-myeloablative conditioning (NMA). Each patient underwent detailed lung function testing (FEV1, FVC, FEV1/FVC, RV, TLC, DLCO and KCO) and measurement of exhaled nitric oxide before HSCT and 3, 6 and 12 months posttransplant. The incidence of pulmonary infections and CMV reactivation were also monitored. This group was compared with another group of 28 patients who underwent the same type of transplantation but without MSC co-infusion. Results: Lung function tests did not show important modifications over time and did not differ between the MSC and control groups. There was a higher 1-year incidence of infection, particularly of fungal infections, in patients having received a MSC co-infusion. There was no difference between groups regarding the 1-year incidence of CMV reactivation. Conclusions: MSC co-infusion does not induce pulmonary deterioration 1 year after HSCT with NMA conditioning. MSC appear to be safe for the lung but close monitoring of pulmonary infections remains essential. [less ▲]

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See detailInfusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ULg; LECHANTEUR, Chantal ULg; Lucas, Sophie et al

in Transfusion (2014), 54(February), 353-363

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See detailEffect of post remission therapy before 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 (2014), 20(2), 202-208

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 detailEffect of post remission therapy before 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 (2014), 20(2), 202-208

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 detailEffect of post remission therapy before 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 (2014), 20(2), 202-208

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 detailEffect of post remission therapy before 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 (2014), 20(2), 202-208

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 detailImmunomodulatory effects of Rapamycin in xenogeneic GVHD
Ehx, Grégory ULg; HANNON, Muriel ULg; DUBOIS, Sophie ULg et al

Poster (2014, January 27)

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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 (2014), 9

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 detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.
Binsfeld, Marilène ULg; BEGUIN, Yves ULg; Belle, Ludovic et al

in Belgian Journal of Hematology (2014)

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See detailMultiple myeloma cells instruct myeloid-derived suppressor cells to release pro-angiogenic cytokines
Binsfeld, Marilène ULg; Heusschen, Roy ULg; Lamour, Virginie et al

in Belgian Journal of Hematology (2014)

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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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