References of "Willems, Evelyne"
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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 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 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 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 detailCotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Baron, Frédéric ULg; Lechanteur, Chantal ULg; Willems, Evelyne ULg et al

in Biology of Blood & Marrow Transplantation (2010), 16(6), 838-47

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD ... [more ▼]

Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe. [less ▲]

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See detailMaladie du greffon contre l'hôte chronique : une prise en charge multidisciplinaire
Servais, Sophie ULg; Willems, Evelyne ULg; Beguin, Yves ULg et al

in Revue Médicale de Liège (2010), 65

Chronic Graft-Versus-Host-Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of ... [more ▼]

Chronic Graft-Versus-Host-Disease (GVHD) is a frequent complication of allogeneic hematopoietic cell transplantation. This review article describes recent advances in the classification and treatment of chronic GVHD. [less ▲]

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See detailWhat Is The Role For Regulatory T-Cells After Nonmyeloablative Conditioning?
Humblet-Baron, S.; CASTERMANS, Emilie ULg; Vanbellinghen, J.-F. et al

in Biology of Blood & Marrow Transplantation (2009, February), 15(2), 122-123

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See detailA prospective randomized multicenter trial of darbepoetin-alfa and I.V. iron administration after autologous hematopoietic stem cell transplantation.
Beguin, Yves ULg; Maertens, J.; DE PRIJCK, Bernard ULg et al

Poster (2009)

We conducted a multicenter prospective randomized study analyzing the impact of darbepoetin alfa (DA) with or mithout i.v. iron on erythroid recovery after autologous HCT.

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See detailCo-transplantation of mesenchymal stem cells might mitigate acute GvHD without abrogating graftversus- tumour alloreactivity after allogeneic transplantation with non-myeloablative conditioning
Baron, Frédéric ULg; WILLEMS, Evelyne ULg; LECHANTEUR, Chantal ULg et al

Conference (2009)

Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that ... [more ▼]

Background: Results of nonmyeloablative HCT in pts with HLA-mismatched donors have been disappointing due to high incidence of graft rejection and severe acute GVHD. Recent studies have suggested that infusion of mesenchymal stem cells (MSC) the day of HCT might promote engraftment and prevent acute GVHD after myeloablative allogeneic HCT. However, some studies suggested that MSC co-infusion might abrogate graft-versus-host alloreactivity and graft-versus-tumor effects. This prompted us to investigate whether MSC infusion a few hours before HCT could allow nonmyeloablative HCT from HLA-mismatched donors to be performed safely (i.e. with a 100-day incidence of nonrelapse mortality < 35%). Methods: 20 patients with hematological malignancies were given MSC (1-2 x 10E6 cells/kg) from third party donors a few hours before PBSC from HLA-mismatched unrelated donors, after conditioning with 2 Gy TBI and fl udarabine 90 mg/m. Postgrafting immunosuppression included tacrolimus (day -3 to +180; tapered by day +365) and mycophenolate mofetil (tid days 0 to +42). HLA-compatibility was assessed at the HLA-A, -B, -C, -DRBI and DQBI loci: 13 pairs were mismatched for at least one HLA class I antigen (including 4 pairs who were also mismatched for 1 HLA-class II antigens (n=3) or 1 HLA-class I allele (n=1)), 1 pair was mismatched for 2 HLA class II alleles, while 6 pairs were mismatched for a single HLA class I (n=3) or HLA class II (n=3) alleles. Results: Median follow-up for surviving patients was 288 (range, 76-571) days. One patient with secondary AML had primary graft rejection, while the remaining 19 patients had sustained engraftment. Median donor T-cell chimerism levels on days 28, 100, 180 and 365 after HCT were 90%, 98%, 96%, and 98%, respectively. Grade II, III and IV acute GVHD were seen in 5, 2 and 1 patients, respectively, while 7 experienced NIH moderate/severe chronic GVHD. Three of 7 patients with measurable disease at transplantation achieved complete remission on days 41, 104 and 353 after HCT. Two patients died of nonrelapse causes on days 74 and 114 after HCT, while 3 died of disease progression. Projected 1-yr overall and progressionfree survivals were 77% and 61%, respectively. Conclusions: HLA-mismatched nonmyeloablative HCT with MSC co-infusion appeared to be safe, with MSC co-infusion possibly mitigating graft-versus-host alloreactivity without abrogating graft-versus-tumor effects. Survival is encouraging. [less ▲]

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See detailNon-myeloablative transplantation with CD8-depleted or unmanipulated peripheral blood stem cells: a phase II randomized trial.
Willems, Evelyne ULg; Baron, Frédéric ULg; Baudoux, Etienne ULg et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2009), 23(3), 608-10

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See detailToxoplasmore cérébrale compliquant une mini-allogreffe de cellules souches hématopoïétiques du sang périphérique
Dugauquier, C.; Bataille, Y.; Willems, Evelyne ULg et al

in Revue Médicale de Liège (2009), 64(7-8), 366-369

We report the occurrence of a cerebral toxoplasmosis 52 days after a non-myeloablative allogeneic stem cell transplantation as treatment for acute myeloid leukemia.

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See detailPulmonary veno-occlusive disease in myeloproliferative disorder.
Willems, Evelyne ULg; Canivet, Jean-Luc ULg; Ghaye, Benoît ULg et al

in European Respiratory Journal (2009), 33(1), 213-216

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The ... [more ▼]

The present study reports a case of biopsy-proven pulmonary veno-occlusive disease as a cause of severe pulmonary hypertension in a patient suffering from a chronic myeloproliferative disorder. The pulmonary disease evolved favourably under treatment with defibrotide, a pro-fibrinolytic medication used in hepatic veno-occlusive disease. [less ▲]

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See detailEvidence for neo-generation of T cells by the thymus after non-myeloablative conditioning.
Castermans, Emilie ULg; Baron, Frédéric ULg; Willems, Evelyne ULg et al

in Haematologica (2008), 93(2), 240-7

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning ... [more ▼]

BACKGROUND: Background and objective. We investigated immune recovery in 50 patients given either unmanipulated or CD8-depleted allogeneic peripheral blood stem cells after non-myeloablative conditioning. DESIGN AND METHODS: Fifty patients were randomized to receive either CD8-depleted (n=22) or non-manipulated (n=28) peripheral blood stem cells. The median patients age was 57 (range 36-69) years. The conditioning regimen consisted of 2 Gy total body irradiation with or without added fludarabine. Twenty patients received grafts from related donors, 14 from 10/10 HLA-allele matched unrelated donors, and 16 from HLA-mismatched unrelated donors. Graft-versus-host disease pro-phylaxis consisted of mycophenolate mofetil and cyclosporine. Immune recovery during the first year after hematopoietic cell transplantation was assessed by flow cytometry phenotyping, analyses of the diversity of the TCRBV repertoire, and quantification of signal-joint T-cell receptor excision circles (sjTREC). RESULTS: CD8-depletion of the graft reduced the recovery of CD8(+) T-cell counts in the first 6 months following transplantation (p<0.0001) but had no significant impact on the restoration of other T-cell subsets. Both sjTREC concentration and CD3(+) T-cell counts increased significantly between day 100 and 365 (p=0.010 and p=0.0488, respectively) demonstrating neo-production of T cells by the thymus. Factors associated with high sjTREC concentration 1 year after transplantation included an HLA-matched unrelated donor (p=0.029), a high content of T cells in the graft (p=0.002), and the absence of chronic graft-versus-host disease (p<0.0001). CONCLUSIONS: Our data suggest that while immune recovery is mainly driven by peripheral expansion of the graft-contained mature T cells during the first months after non-myeloablative transplantation, T-cell neo-generation by the thymus plays an important role in long term immune reconstitution in transplanted patients. [less ▲]

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See detailActualités thérapeutiques en hématologie.
De Prijck, Bernard ULg; Baron, Frédéric ULg; Beguin, Yves ULg et al

in Revue Médicale de Liège (2007), 62(5-6), 384-90

This article focuses on recent advances in four important areas of hematology: aggressive lymphomas, allogeneic hematopoietic stem cell transplantation, multiple myeloma, and molecular therapy of cancer.

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