References of "Beguin, Yves"
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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 American Journal of Transplantation (2015, May), 15(suppl 3),

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

Poster (2015, March 27)

Transplanted patients have to deal with numerous side effects of life-long dependence on immunosuppressive drugs. Paradoxically these drugs fail to prevent acute and/or chronic rejection in many cases ... [more ▼]

Transplanted patients have to deal with numerous side effects of life-long dependence on immunosuppressive drugs. Paradoxically these drugs fail to prevent acute and/or chronic rejection in many cases. Mesenchymal stromal cells (MSC) are multipotent and self-renewing bone marrow progenitors that have been shown both in vitro and in vivo as capable of (i) immunomodulation, (ii) anti-inflammation in case of ischemia/reperfusion injury, and (ii) stimulation of tissue repair. MSC could therefore be very interesting in organ recipients to limit chronic graft damage and to allow tolerance. This study aimed to be the first clinical evaluation of the safety and tolerability of MSC infusion after liver transplantation in a prospective, controlled, phase I study. Clinical grade MSCs were locally collected from the bone marrow of unrelated healthy donors. They were cultured in a GMP-compliant lab, underwent extensive quality controls and were frozen for storage in a MSC bank. When needed for patient treatment, MSC were thawed and intravenously injected into patients. 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5-3x106/kg MSC on post- operative day 3 ± 2. These patients were prospectively compared to a group of 10 control (MSC-) 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. 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. This phase I 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. [less ▲]

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See detailImaging myeloma and related monoclonal plasma cell disorders using MRI, low dose whole-body CT and FDG PET/CT
WITHOFS, Nadia ULg; NANNI, C.; SIMONI, Paolo ULg et al

in Clinical and Translational Imaging (2015), 3

A majority of multiple myeloma patients present with osteolytic bone lesions that can cause bone pain, fractures or hypercalcaemia. Correct identification of these lesions is important in the initial ... [more ▼]

A majority of multiple myeloma patients present with osteolytic bone lesions that can cause bone pain, fractures or hypercalcaemia. Correct identification of these lesions is important in the initial assessment of the disease. <br />Although the radiological skeletal survey is the gold standard to detect bone osteolytic lesions, it may miss small bone lesions or lesions located in the spine or pelvis due to the superimposed images of soft tissues. These limitations propelled newer imaging techniques such as positron emission tomography combined with computed tomography (PET/CT) and magnetic resonance imaging (MRI) in the diagnosis of multiple myeloma. In addition, 18F-fluorodeoxyglucose PET/CT and MRI have prognostic value and can be used to monitor disease. <br />This review discusses the additional value of PET/CT and MRI in the management of MM. [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 Acta Gastro-Enterologica Belgica (2015, March), 78(1), 29

Background: Mesenchymal stromal cells (MSC) are multipotent bone marrow 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 marrow 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. 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. Patients & Methods: Clinical grade MSCs were locally collected from the bone marrow of unrelated healthy donors. They were cultured in a GMP-compliant lab, underwent extensive quality controls and were frozen for storage in a MSC bank. When needed for patient treatment, MSC were thawed and intravenously injected into patients. 10 liver transplant recipients under standard immunosuppression (TAC-MMF-low dose steroids until day 30) received 1.5-3x106/kg MSC on post-operative day 3±2. These patients were prospectively compared to a group of 10 control (MSC-) 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. [less ▲]

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See detailAzacytidine prevents experimental sclerodermic chronic graft-versus-host disease
Fransolet, Gilles ULg; Ehx, Grégory ULg; SOMJA, Joan ULg et al

Poster (2015, January 30)

Introduction: Graft-versus-host disease (GVHD) remains one major complication of allogeneic hematopoietic stem cell transplantation (HSCT). Following unmanipulated peripheral-blood stem cell ... [more ▼]

Introduction: Graft-versus-host disease (GVHD) remains one major complication of allogeneic hematopoietic stem cell transplantation (HSCT). 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 role in the pathology of chronic GVHD by inhibiting alloreactive conventional T cells. Several studies have shown the hypomethylating agent Azacytidine (Aza) can demethylate the master transcription factor of Treg (Forkhead box protein 3 factor, FoxP3), thus promoting Treg differentiation of conventional T cells. This work investigates the impact of Aza in a classical murine model of sclerodermic chronic GVHD (B10.D2  BALB/cJ). Methods: Lethally irradiated BALB/cJ recipient mice were injected with 107 bone marrow cells + 7.107splenocytes from B10.D2 donor mice. Recipients were treated with subcutaneous injections of Aza at the dose of 0,5 or 2 mg/kg every two days from day 10 to 30 following transplantation. Mice GVHD was evaluated with five criteria (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). Results: Mice treated with Aza 0.5 mg/kg (n = 14) or 2 mg/kg (n = 17) had significant lower clinical scores compared to control ones (n = 15) 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 (P = 0.047), as well as a higher percentage of Tregs expressing the KI67 proliferative marker on the same day (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 (P = 0.05). Conclusion : Aza prevented sclerodermic GVHD in this classical murine model of chronic GVHD. [less ▲]

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See detailCircadian and circannual variations in cord blood hematopoietic cell composition
Servais, Sophie ULg; BAUDOUX, Etienne ULg; Brichard, B. et al

in Haematologica (2015), 100(1), 32-34

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See detailValidation of a multicolor staining to monitor phosphoSTAT5 levels in regulatory T-cell subsets
Ehx, Grégory ULg; Hannon, Muriel ULg; BEGUIN, Yves ULg et al

in Oncotarget (2015), 6

BACKGROUND: Regulatory T cells (Tregs) are key players in immune tolerance. They express the transcription factor FOXP3 and are dependent of the STAT5 signaling for their homeostasis. So far, the study of ... [more ▼]

BACKGROUND: Regulatory T cells (Tregs) are key players in immune tolerance. They express the transcription factor FOXP3 and are dependent of the STAT5 signaling for their homeostasis. So far, the study of phosphorylated epitopes by flow cytometry required treating the cells with methanol, which is harmful for several epitopes. METHODS: Here we assessed whether the PerFix EXPOSE reagent kit (PFE) (Beckman Coulter) allowed monitoring the phosphorylation level of STAT5 in Treg subpopulations together with complex immunophenotyping. Results observed with the PFE kit were compared to those observed without cell permeabilization for surface markers, with paraformaldehyde permeabilization for non-phosphorylated intracellular epitopes, and with methanol-based permeabilization for phosphoSTAT5 staining. RESULTS: In human PBMCs, the PFE kit allowed the detection of surface antigens, FOXP3, KI67 and phosphoSTAT5 in similar proportions to what was observed without permeabilization (for surface antigens), or with PFA or methanol permeabilizations for FOXP3/KI67 and phosphoSTAT5, respectively. Comparable observations were made with murine splenocytes. Further, the PFE kit allowed determining the response of different human and murine Treg subsets to IL-2. It also allowed demonstrating that human Treg subsets with the highest levels of phosphoSTAT5 had also the highest suppressive activity in vitro, and that anti-thymocyte glogulin (ATG) induced Treg independently of the STAT5 pathway, both in vitro and in vivo. CONCLUSIONS: We have validated a multicolor staining method that allows monitoring phosphoSTAT5 levels in Treg subsets. This staining could be useful to monitor responses of various Treg subsets to IL-2 therapy. [less ▲]

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See detailPrise en charge actuelle du lymphome de la zone marginale
Bonnet, Christophe ULg; LEJEUNE, Marie ULg; VAN KEMSEKE, Catherine ULg et al

in Revue Médicale Suisse (2015), 11

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See detailContribution of Revised International Prognostic Scoring System Cytogenetics to Predict Outcome After Allogeneic Stem Cell Transplantation for Myelodysplastic Syndromes: A Study From the Société Française de Greffe de Moelle et Thérapies Cellulaires
Gauthier, Jordan; Damaj, Gandhi; Langlois, Carole et al

in Transplantation (2015), 99(8), 1672-1680

Background. The prognosis of myelodysplastic syndromes (MDS) after allogeneic stem cell transplantation is critically determined by cytogenetic abnormalities, as previously defined by International ... [more ▼]

Background. The prognosis of myelodysplastic syndromes (MDS) after allogeneic stem cell transplantation is critically determined by cytogenetic abnormalities, as previously defined by International Prognostic Scoring System (IPSS) cytogenetics. It has been shown that a new cytogenetic classification, included in the IPSS-R (cytogenetic-IPSS-R [C-IPSS-R]), can better predict the outcome of untreated MDS patients.Methods. In this study, we assessed the impact of the IPSS-R cytogenetic score (C-IPSS-R) on the outcome of 367 MDS patients transplanted from HLA-identical siblings or HLA allele-matched unrelated donors. Results. According to the C-IPSS-R, 178 patients (48%) fell in the good risk, 102 (28%) in the intermediate risk, 77 (21%) in the poor risk, and 10 (3%) in the very poor risk group. In multivariate analysis, after a median follow-up of 4 years, the poor and very poor-risk categories correlated with shorter overall survival (OS) (4-year OS, 32%; hazard ratio [HR], 1.59; P = 0.009 and OS, 10%; HR, 3.18; P = 0.002, respectively) and higher cumulative incidence of relapse (CIR) (CIR, 52%; HR, 1.82; P = 0.004 and CIR, 60%; HR, 2.44; P = 0.060, respectively). Conclusions. Overall, the C-IPSS-R changed the IPSS cytogenetic risk only in 8% of cases but identified a new risk group, the very poor C-IPSS-R category, with dismal outcome after allogeneic stem cell transplantation (10% 4-year OS, 60% 4-year CIR). Posttransplantation maintenance therapy should be investigated in prospective trials for patients with high-risk C-IPSS-R karyotypes. [less ▲]

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See detailAllogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy
Halet, JP.; Michael, W.; Schüpbach, W. et al

in Brain : A Journal of Neurology (2015), 138

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that ... [more ▼]

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10–41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262–1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus 510/10) and disease characteristics (liver disease, history of gastrointestinal pseudoobstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor. [less ▲]

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See detailBHS guidelines for the treatment of Burkitt lymphoma
BONNET, Christophe ULg; Janssens, A.; Wu, KL. et al

in Belgian Journal of Hematology (2015), 6(2), 61-69

Burkitt lymphoma (BL) is a rare but very aggressive non-Hodgkin’s lymphoma characterized by an isolated translocation t(8;14)(q24;q32). The sporadic form is the subentity most frequently encountered in ... [more ▼]

Burkitt lymphoma (BL) is a rare but very aggressive non-Hodgkin’s lymphoma characterized by an isolated translocation t(8;14)(q24;q32). The sporadic form is the subentity most frequently encountered in our country. Diagnosis and initial work-up must be completed rapidly to start treatment as soon as possible. Positron emission tomography (PET) scan is useful for initial staging and to evaluate the chemosensitivity of the tumor during and after treatment. After debulking, it is recommended to add rituximab to chemotherapy. Currently intensive short-cycle chemotherapies (ISCC) and low intensity chemotherapies (LIC) are two valuable options. Radiotherapy is not indicated except in case of central nervous system involvement. Patients achieving complete remission must be followed carefully during the first year to detect recurrence of the disease. More than 80% of patients sustain their remission one year following initial treatment and are considered cured. For patients in partial remission or with chemosensitive relapse, autologous stem cell transplantation is recommended following re-induction with non-cross-resistant polychemotherapy. Monitoring complete blood counts and cognitive functions is important to detect late toxicity of the applied therapies. [less ▲]

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See detailImpact of graft source and composition on outcomes after allogeneic stem cell transplantation
SERVAIS, Sophie ULg; Baron, Frédéric ULg; BEGUIN, Yves ULg

in Belgian Journal of Hematology (2015), 6(4), 162-168

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See detailImpact of Pre-Transplant Anti-T Cell Globulin (ATG) on Immune Recovery after Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation.
SERVAIS, Sophie ULg; Menten-Dedoyart, Catherine; Beguin, Yves ULg et al

in PloS one (2015), 10(6), 0130026

BACKGROUND: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation ... [more ▼]

BACKGROUND: Pre-transplant infusion of rabbit anti-T cell globulin (ATG) is increasingly used as prevention of graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). However, the precise impact of pre-transplant ATG on immune recovery after PBSCT is still poorly documented. METHODS: In the current study, we compared immune recovery after myeloablative PBSCT in 65 patients who either received (n = 37) or did not (n = 28) pre-transplant ATG-Fresenius (ATG-F). Detailed phenotypes of circulating T, B, natural killer (NK) and invariant NKT (iNKT) cells were analyzed by multicolor flow cytometry at serial time-points from day 40 to day 365 after transplantation. Thymic function was also assessed by sjTREC quantification. Serious infectious events were collected up to 2 years post-transplantation. RESULTS: Pre-transplant ATG-F had a prolonged (for at least up to 1-year) and selective negative impact on the T-cell pool, while it did not impair the recovery of B, NK nor iNKT cells. Among T cells, ATG-F selectively compromised the recovery of naive CD4+, central memory CD4+ and naive CD8+ cells, while it spared effector memory T and regulatory T cells. Levels of sjTRECs were similar in both cohorts at 1-year after PBSCT, suggesting that ATG-F unlikely impaired thymopoiesis at long-term after PBSCT. Finally, the incidence and rate of serious infections were similar in both groups, while ATG-F patients had a lower incidence of grade II-IV acute graft-versus-host disease. CONCLUSIONS: Pre-transplant ATG-F induces long-lasting modulation of the circulating T-cell pool after myeloablative PBSCT, that may participate in preventing graft-versus-host disease without deeply compromising anti-pathogen defenses. [less ▲]

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