References of "BEGUIN, Yves"
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See detailThe use of mesenchymal stromal cells in solid organ transplantation
GREGOIRE, Céline ULg; DETRY, Olivier ULg; Jouret, François ULg et al

in The Biology and Therapeutic Applications of Mesenchymal Cells (in press)

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See detailThe role of mesenchymal stem cells in the treatment of ulcerative colitis and Crohn's disease
GREGOIRE, Céline ULg; Louis, Edouard ULg; BRIQUET, Alexandra ULg et al

in The Biology and Therapeutic Applications of Mesenchymal Cells (in press)

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See detailNovel approaches for preventing acute graftversus- host disease after allogeneic hematopoietic stem cell transplantation
SERVAIS, Sophie ULg; BEGUIN, Yves ULg; Delens, Loïc ULg et al

in Expert Opinion on Investigational Drugs (2016)

Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success ... [more ▼]

Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor’s immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40–60% of alloHSCT recipients. Areas covered In this review, after a brief summary of current knowledge on the pathogenesis of aGVHD, the authors review the current combination of a calcineurin inhibitor with an antimetabolite with or without added anti-thymocyte globulin (ATG) and emerging strategies for GVHD prevention. Expert opinion A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGVHD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects. [less ▲]

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See detailGalectin-1 is involved in osteoclast biology
Muller, Joséphine ULg; Binsfeld, Marilène ULg; DUBOIS, Sophie ULg et al

Poster (2016, February 28)

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See detailSalt but not glucocorticoïds enhances Th17 differentiation from naïve T cells in vitro
Delens, Loïc ULg; SERVAIS, Sophie ULg; Vrancken, Louise et al

Poster (2016, January 29)

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See detailThe Changing Landscape of Smoldering Multiple Myeloma: A European Perspective
CAERS, Jo ULg; de Larrea, Carlos; Leleu, Xavier et al

in Oncologist (2016), 21

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathyof undeterminedsignificance tomultiplemyeloma(MM), based on higher levels of circulating ... [more ▼]

Smoldering multiple myeloma (SMM) is an asymptomatic clonal plasma cell disorder and bridges monoclonal gammopathyof undeterminedsignificance tomultiplemyeloma(MM), based on higher levels of circulating monoclonal immunoglobulin and bone marrow plasmocytosis without end-organ damage. Until a Spanish study reported fewer MM-related events and better overall survival among patients with highrisk SMM treated with lenalidomide and dexamethasone, prior studies had failed to show improved survival with earlier intervention, although a reduction in skeletal-related events (without any impact on disease progression) has been described with bisphosphonate use. Risk factors have now been defined, and a subset of ultra-high-risk patients have been reclassified by the International Myeloma Working Group asMM, and thus will require optimalMMtreatment, based on biomarkers that identify patients with a.80% risk of progression. The number of these redefined patients is small (∼10%), but important to unravel, because their risk of progression to overt MM is substantial ($80% within 2 years). Patients with a high-risk cytogenetic profile are not yet considered for early treatment, because groups are heterogeneous and risk factors other than cytogenetics are deemed to weight higher. Because patients with ultra-highrisk SMM are now considered as MMand may be treated as such, concerns exist that earlier therapy may increase the risk of selecting resistant clones and induce side effects and costs. Therefore, an even more accurate identification of patients who would benefit from interventions needs to be performed, and clinical judgment and careful discussion of pros and cons of treatment initiation needs to be undertaken. For the greater majority ofSMMpatients, the standard of care remains observation until development of symptomatic MM occurs, encouraging participation in ongoing and upcoming SMM/early MM clinical trials, as well as consideration of bisphosphonate use in patients with early bone loss. [less ▲]

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See detailYellow nail syndrome after allogeneic haematopoietic stem cell transplantation in two patients with multiple myeloma
Grégoire, Céline ULg; GUIOT, Julien ULg; Vertenoeil, Gaëlle ULg et al

in Acta Clinica Belgica (2016)

Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have ... [more ▼]

Objective and Importance: Yellow nail syndrome (YNS) is a rare disorder of unknown aetiology characterized by the triad of yellow nails, lymphoedema and respiratory manifestations. About 200 cases have been reported, but a lot of patients probably elude proper diagnosis because of both variability of symptoms and ignorance of this syndrome by many physicians. The pathogenesis remains unclear, and could involve functional lymphatic abnormalities, microvasculopathy or lymphocyte deficiency, but none of these hypotheses seems fully satisfactory. Clinical Presentation: We report for the first time two cases of YNS associated with multiple myeloma relapsing after non-myeloablative haematopoietic cell transplantation (HCT). In these two cases, onset or worsening of YNS symptoms followed graft-versus-host disease (GvHD) manifestations. Intervention: Corticosteroids given to treat GvHD also improved YNS manifestations. Conclusion: YNS after HCT might be a microvascular manifestation of endothelial GvHD and corticosteroids might be an effective treatment. [less ▲]

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See detailFamilial thyrogastric autoimmune syndrome : a study of 22 kindreds
Sid, Sélim ULg; LUTTERI, Laurence ULg; BEGUIN, Yves ULg et al

in Abstract book - 20th Annual Congress of the Belgian Society of Internal Medicine (2015, December)

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See detailL'Azacytidine comme traitement de la maladie du greffon contre l'hôte de type chronique sclérodermique expérimentale.
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

Conference (2015, November 19)

Introduction: Graft-versus-host disease (GVHD) has remained a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) for the last decades. Following unmanipulated peripheral-blood ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) has remained a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) for the last decades. Following unmanipulated peripheral-blood stem cell transplantation, 60% of the patients experience chronic GVHD while approximately 15% of them develop a sclerodermic form of chronic GVHD characterized by multiple organ fibrosis and loss of skin elasticity. Regulatory T cells (Tregs) play a pivotal protective role in the pathogenesis of chronic GVHD by inhibiting alloreactive conventional T cells (Tconvs). Several studies have shown that hypomethylating agents such as azacytidine (Aza) can demethylate the master transcription factor of Treg (Forkhead box protein 3 factor, FoxP3), thus promoting Treg differentiation from Tconvs. This work investigates the impact of Aza in a classical murine model of sclerodermic chronic GVHD (B10.D2  BALB/cJ). Methods: In vitro analyses have been performed to determine the impact of Aza on collagen production. NIH-3T3 fibroblastic cells were plated and stimulated with 50 ng of PDGF or 10 ng of TGF-beta. Cells were then cultured with various concentrations of Aza for 48 hours. After culture, cells were stained with Sirius Red before quantification of collagen amount by absorbance at 490 nm. For in vivo experiments, lethally irradiated (7 Gy) BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107splenocytes from B10.D2 donor mice to induce scl-cGVHD. Recipients were injected with either 0,5 or 2 mg/kg of Aza every 48 hours from day 10 to 30 following transplantation. GVHD was scored using a five criteria scale (weight loss, activity, fibrosis, hair loss and mice posture; 0-1-2 points/criteria). Mice were sacrificed at a score of 8/10 (or > 20% weight loss) or at day 52 after transplantation (end of experiment). Results: Concerning in vitro analyses, results suggest a decreased production of collagen at higher concentration of Aza with both stimulations (seen by a gradual diminution of absorbance). For in vivo experiments, mice treated with Aza 0.5 mg/kg (n = 14) or 2 mg/kg (n = 25) had significant lower clinical scores of GVHD compared to control ones (n = 23) after treatment. FACS analysis showed a higher proportion of Treg among CD4+ T cells in the blood of Aza 2 mg/kg mice than in control mice at day 35 following transplantation (P = 0.047), as well as a higher percentage of Tregs expressing the KI67 proliferative marker on the same time point (P = 0.0005). Finally, analyses of the cellular blood components with Cell-dyn demonstrated that Aza 2 mg/kg treated mice were significantly lymphopenic as compared to control mice at day 35 after transplantation (P = 0.05). Conclusion : Aza prevented sclerodermic GVHD in this classical murine model of chronic GVHD. [less ▲]

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See detailThird-party mesenchymal stem cell infusion in kidney transplant recipient: 6-month safety interim analysis
WEEKERS, Laurent ULg; ERPICUM, Pauline ULg; DETRY, Olivier ULg et al

in Transplant International (2015, November), 28(S4), 223-224278

Background: Mesenchymal stromal cell (MSC) have immunomodulating properties and could be used as immunosuppressive agents. We report the 6- month safety results for the 5 first patients treated with MSC ... [more ▼]

Background: Mesenchymal stromal cell (MSC) have immunomodulating properties and could be used as immunosuppressive agents. We report the 6- month safety results for the 5 first patients treated with MSC after kidney transplantation (KTx). Here, we address 3 specific safety issues: immunization against MSC and engraftment syndrome defined as acute graft dysfunction not related to rejection and over-immunosuppression. Patients and method: MSC production was carried out locally. MSC were not matched with kidney recipients’ HLA. Included patients were non-immunized, first transplant recipients from deceased donors. MSC (1.5–3.0 9 106/kg) infusion was planned 3 to 5 days post KTx. Patients with cardiovascular instability post KTx were excluded. All patients were treated with Basiliximab induction, Tacrolimus, Mycophenolate Mofetil and Steroid. We prospectively screened for anti-HLA antibodies at month 1, 3 and 6. Informed consent was obtained from all participants. The local ethical committee approved the protocol. Results: Collectively there were 23/50 and 29/50 HLA mismatches (MM) with kidney and MSC donor respectively, out of which 5 were shared MM. One patient developed de novo DSA, 2 patients anti-HLA antibodies against shared kidney/MSC MM and 1 patient developed 2 specific antibodies against MSC (MSCSA) at month 6. All antibodies were anti HLA class I except for 1. We did not observe any “engraftment” syndrome. Three patients experienced non- severe opportunistic infections: 1 CMV reactivation and 2 polyoma-BK virus viremia.Conclusion: We did not observe any strong safety signal. We did however observe some degree of immunization in 3 patients: 2 developed antibodies against shared kidney/MSC donor HLA MM and 1 MSCSA. [less ▲]

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See detailInfusion of third-party mesenchymal stream cells after liver transplantation: a phase-1, open-label, clinical study
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Transplant International (2015, November), 28(S4), 1027

Background: Mesenchymal stromal cells (MSC) are multipotent bone mar- row progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are multipotent bone mar- row progenitors that have demonstrated significant immunosuppressive effects in various in vivo and in vitro studies. This study aimed to be the first evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled phase-1 study. Methods: 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5–3 9 106/kg third party MSC on post-operative day 3 ` 2. These patients were prospectively compared to a group of 10 control liver recipients. Primary endpoints were MSC infusion toxicity, and incidence of cancer and opportunistic infections at month 6. Secondary endpoints were patient and graft survivals and rejection at month 6, as well as the effects of MSC on recipients’ immune function and on immunohistology of at month 6 graft biopsies. Results: No MSC infusional toxicity was observed. Both groups were comparable in terms of donor and recipient characteristics. There was no difference in primary end-points between control and MSC groups. No patient developed de novo cancer. There was no statistical difference in patient and graft survivals or in rejection rates. There was no graft rejection in the MSC group. Month-6 graft biopsies were not different according to Banff and fibrosis scores. Discussion: This phase 1 study showed excellent tolerability and safety of a single infusion of third-party MSC after liver transplantation. There were no graft safety issues and no excess of immunosuppression after MSC injection. Further analyses of consequences of MSC injection on the immune profile are needed. The possibility of avoiding calcineurin-inhibitors with repeated MSC injections as main immunosuppressive therapy and/of tolerance induction by MSC infusion should be investigated by further studies. This study is in part supported by an ESOT Senior Clinical Research Grant and by the University of Liege. [less ▲]

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See detailImmune Recovery after Allogeneic Hematopoietic Stem Cell Transplantation following Flu-TBI versus TLI-ATG Conditioning
HANNON, Muriel ULg; BEGUIN, Yves ULg; Ehx, Grégory ULg et al

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2015), 21(14), 3131-9

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft ... [more ▼]

Purpose: A conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) combining total lymphoid irradiation (TLI) plus anti-thymocyte globulin (ATG) has been develop to induce graft-versus-tumor effects without graft-versus-host disease (GVHD). Experimental Design: We compared immune recovery in 53 patients included in a phase II randomized study comparing nonmyeloablative HCT following either fludarabine plus 2 Gy total body irradiation (TBI arm, n=28) or 8 Gy TLI plus anti-thymocyte globulin (TLI arm, n=25). Results: In comparison to TBI patients, TLI patients had a similarly low 6-month incidence of grade II-IV acute GVHD, a lower incidence of moderate/severe chronic GVHD (P=0.02), a higher incidence of CMV reactivation (P<0.001), and a higher incidence of relapse (P=0.01). While recovery of total CD8+ T cells was similar in the two groups, with median CD8+ T cell counts reaching the normal values 40-60 days after allo-HCT, TLI patients had lower percentages of naïve CD8 T cells. Median CD4+ T cell counts did not reach the lower limit of normal values the first year after allo-HCT in the two groups. Further, CD4+ T cell counts were significantly lower in TLI than in TBI patients the first 6 months after transplantation. Interestingly, while median absolute regulatory T cell (Treg) counts were comparable in TBI and TLI patients, Treg/naïve CD4+ T cell ratios were significantly higher in TLI than in TBI patients the 2 first years after transplantation. Conclusions: Immune recovery differs substantially between these two conditioning regimens possibly explaining the different clinical outcomes observed (NCT00603954). [less ▲]

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