References of "Beguin, Yves"
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See detailClinical - scale expansion of mesenchymal stromal cells: a large banking experience
LECHANTEUR, Chantal ULg; BRIQUET, Alexandra ULg; GIET, Olivier ULg et al

in Journal of Translational Medicine (2016), 14

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the ... [more ▼]

Background: Mesenchymal stromal cells (MSC) are largely investigated in clinical trials aiming to control inappropriate immune reactions (GVHD, Crohn’s disease, solid organ transplantation). As the percentage of MSC precursors in bone marrow is very low, these must be expanded in vitro to obtain therapeutic cell doses. We describe here the constitution of an allogeneic human third-party MSC bank from screened healthy volunteer donors in compliance with quality specifications and ISCT-release criteria and report follow-up of different aspects of this activity since 2007. Methods: 68 clinical-grade large-scale MSC cultures were completed and analyzed. The whole process was described, including volunteer donor screening, bone marrow collection, mononuclear cell isolation and expansion over 4 weeks, harvesting, cryopreservation, release, administration and quality controls of the cells (including microbiology, phenotype, and potency assays). Results: From 59 validated donors, 68 cultures were completed (mean of final yields: 886 × 106 cells/culture) and a total of 464 MSC aliquots have been produced and stored in liquid nitrogen (mean of 132.8 × 106 cells/bag). Each MSC batch underwent extensive testing to verify its conformity with EBMT and ISCT release criteria and was individually validated. As of June 1 2015, 314 bags have been released and infused to patients included in 6 different clinical protocols. All thawed MSC units satisfied to release criteria and no infusion-related toxicity was reported. Conclusion: In conclusion, despite low passage cultures, we have been able to create an allogeneic “off-the-shelf” MSC bank with a large number of frozen aliquots and report here an efficient clinical-grade MSC banking activity in place for more than 7 years. Our challenge now is to produce MSC in compliance with good manufacturing practices (GMP) as, in the meantime, MSC have become considered as advanced therapy medicinal products (ATMP). Another significant challenge remains the development of relevant potency assay. [less ▲]

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See detailLe syndrome thyro-gastrique auto-immun : actualités cliniques et thérapeutiques
VALDES SOCIN, Hernan Gonzalo ULg; SID, Sélim ULg; LUTTERI, Laurence ULg et al

in Vaisseaux, Coeur, Poumons (2016), 21(4), 40-45

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See detailEffet of immune modulation in relapsed peripheral T cell lymphomas after allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Mamez; Levy, V; Chevallier, P et al

in Bone Marrow Transplantation (2016), 51

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell ... [more ▼]

Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with nonimmunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68–48.21), P = 0.0009) and skin relapse (odds ratio: 4.15 (1.04–16.50), P = 0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17–0.640), P = 0.0009). This large series provides encouraging evidence of a true GvL effect in this disease. [less ▲]

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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 detailManagement of myelodysplasic syndrome relapsing after allogeneic hematopoietic stem cell transplantation: a study by the French Society of Bone Marrow Transplantation and Cell Therapies
Guièze, R; Damaj, G; Pereira, B et al

in Biology of Blood & Marrow Transplantation (2016), 22

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT ... [more ▼]

To find out prognostic factors and to investigate different therapeutic approaches, we report on 147 consecutive patients who relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndrome (MDS). Sixty-two patients underwent immunotherapy (IT group, second allo-HSCT or donor lymphocyte infusion), 39 received cytoreductive treatment alone (CRT group) and 46 were managed with palliative/supportive cares (PSC group). Two-year rates of overall survival (OS) were 32%, 6%, and 2% in the IT, CRT, and PSC groups, respectively (P < .001). In multivariate analysis, 4 factors adversely influenced 2-year rates of OS: history of acute graft-versus-host disease (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.26 to 2.67; P ¼ .002), relapse within 6 months (HR, 2.69; 95% CI, .82 to 3.98; P < .001), progression to acute myeloid leukemia (HR, 2.59; 95% CI, 1.75 to 3.83; P < .001), and platelet count < 50 G/L at relapse (HR, 1.68; 95% CI, 1.15 to 2.44; P ¼.007). A prognostic score based on those factors discriminated 2 risk groups with median OSs of 13.2 versus 2.4 months, respectively (P < .001). When propensity score, prognostic score, and treatment strategy were included in Cox model, immunotherapy was found to be an independent factor that favorably impacts OS (HR, .40; 95% CI, .26 to .63; P < .001). In conclusion, immunotherapy should be considered when possible for MDS patients relapsing after allo-HSCT. [less ▲]

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

Poster (2016)

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See detailadministration of Third-Party Mesenchymal Stromal Cells at the Time of Kidney Transplantation: Interim Safety Analysis at One-Year Follow-Up
WEEKERS, Laurent ULg; Erpicum, Pauline ULg; DETRY, Olivier ULg et al

in Transplant International (2016), 29(Suppl 2), 13-6

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx ... [more ▼]

Objective. Mesenchymal stromal cells (MSC) therapy has been suggested in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC at the time of KTx. Methods. On postoperative day 3 (D3), third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recipients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. In parallel, 7 comparable KTx recipients were included as controls. Written informed consent was obtained from all participants. Results. No hemodynamic or immune-allergic side-effect was noted at the time of MSC injection. Still, 1 patient with a history of ischemic heart disease had a NSTEMI ~3h after MSC infusion. Four MSC patients presented with CMV reactivation within 165 ± 96 days post KTx, whereas 3 controls had positive polyoma-BK viremia within 92 ± 4d post KTx. Three MSC patients were affected by pneumonia within 269 ± 98d post KTx, whereas 3 controls had urinary infection within 48 ± 43d post KTx. No MSC engraftment syndrome was observed. At D14, eGFR in MSC and control groups was 47.1 ± 6.8 and 39.7 ± 5.9 ml/min, respectively (p, 0.05). At 1 year, eGFR in MSC and control groups was 43.1 ± 17.8 and 53.9 ± 13.4 ml/min, respectively (p, 0.25). At 3-month protocol biopsy, no rejection was evidenced in MSC or control patients. Later on, 1 acute rejection was diagnosed at D330 in 1 MSC patient. No biopsy-proven AR was noted in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches. Conclusions. MSC infusion was safe in all patients except one. Incidence of opportunist and non-opportunist infections was similar in both MSC and control groups. No MSC engraftment syndrome was documented. No difference in eGFR was found at 1 year post KTx. Putative immunization against MSC was observed in 3 patients. [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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