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See detailFocus sur les lymphocytes T dans la maladie du greffon contre l'hôte après allogreffe de cellules soucges hématopoïétiques: implications pour de nouvelles stratégies de prévention
Vrancken, L; Delens, Loïc ULg; BEGUIN, Yves ULg et al

in Oncol. Hematol. (in press)

Malgré les stratégies de prévention actuelles, la maladie du greffon contre l’hôte (greffe-versus-hôte, GVH) aiguë (GVHa) reste une complication sévère et fréquente de l’allogreffe de cellules souches ... [more ▼]

Malgré les stratégies de prévention actuelles, la maladie du greffon contre l’hôte (greffe-versus-hôte, GVH) aiguë (GVHa) reste une complication sévère et fréquente de l’allogreffe de cellules souches hématopoïétiques. Bien que la physiopathologie de celle-ci ne reste que partiellement élucidée à ce jour, il est classiquement admis que les lymphocytes T (LT) jouent un rôle important dans son processus biologique. Les progrès récents de l’immunologie des LT dans la GVHa ont permis de diversifier les pistes visant à prévenir la survenue de cette complication post-greffe. Plusieurs approches sont en cours d’exploration dans des essais cliniques avec des résultats encourageant tels que la manipulation ex vivo des LT avant leur transfert chez le patient afin de leur faire exprimer des gènes suicide, l’élimination in vivo des LT proliférant directement après la greffe, l’inhibition de l’activation des LT en interférant avec les voies de signalisation en aval du TCR ou celles induites par les cytokines, l’induction de l’anergie des LT en bloquant les signaux de costimulation, le blocage de l’adressage des LT vers les organes lymphoïdes secondaires et les tissus cibles, la promotion de l’immunotolérance par la perfusion de lymphocytes T régulateurs ou par l’utilisation d’agents favorisant leur différenciation et leurs fonctions in vivo et la modulation de l’expression génique des cellules immunitaires par des modulateurs épigénétiques. Outre la prévention de la GVHa, le défi des nouvelles stratégies consiste également à ne pas compromettre l’effet bénéfique de la greffe contre la tumeur ni la reconstitution des défenses anti-infectieuses. [less ▲]

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See detailXenogeneic graft-versus-host disease : Impact of Th17 cells
Delens, Loïc ULg; SERVAIS, Sophie ULg; Vrancken, Louise ULg et al

Poster (2017, March 27)

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See detailXenogeneic graft-versus-host disease: Impact of Th17 cells.
Delens, Loïc ULg; SERVAIS, Sophie ULg; Vrancken, Louise et al

Poster (2016, December 08)

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See detailAlterations of circulating lymphoid committed progenitor cellular metabolism after allogeneic stem cell transplantation in humans
GLAUZY; PEFFAULT DE LATOUR; ANDRE-SCHMUTZ et al

in Experimental Hematology (2016), 44(9), 811-816

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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), 9

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 detailResponse to antiviral therapy in haematopoietic stem cell transplant recipients with cytomegalovirus (CMV) reactivation according to the donor CMV serological status.
SERVAIS, Sophie ULg; DUMONTIER, Nicolas; BIARD, L. et al

in Clinical Microbiology and Infection (2016), 22(3), 2891-7

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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 detailMultipotent mesenchymal stromal cell therapy for steroid-refractory acute graft-versus-host disease after allogeneic stem cell transplantation
SERVAIS, Sophie ULg; GREGOIRE, Céline ULg; BARON, Frédéric ULg et al

in Belgian Journal of Hematology (2016), 7

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not ... [more ▼]

Steroid-refractory acute graft-versus-host disease is a severe complication after allogeneic stem cell transplantation. So far, its treatment remains very challenging since the current therapies do not offer significant benefits. Among the most recent approaches, multipotent mesenchymal stromal cell-based therapy has attracted great interest over the past decade. Here, we briefly reviewed the current knowledges about the immunomodulatory properties of multipotent mesenchymal stromal cells as well as results of preclinical and clinical studies having assessed their efficacy to modulate steroid-refractory acute graft-versus-host disease. [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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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 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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See detailLong term Immune Reconstitution and infection burden after Mismatched Hematopoietic Stem Cell Transplantation
SERVAIS, Sophie ULg; Lengline, Etienne; Porcher, Raphael et al

in Biology of Blood & Marrow Transplantation (2014), 20(4), 507-517

Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long lasting immune deficiency ... [more ▼]

Mismatched unrelated donor (MMUD) or umbilical cord blood (UCB) can be chosen as alternative donors for allogeneic stem cell transplantation but might be associated with long lasting immune deficiency. Sixty-six patients who underwent a first transplantation from either UCB or 9/10 MMUD (n= 36) and who survived beyond 3 months were evaluated. Immune reconstitution was prospectively assessed at sequential time points after transplantation. NK, B, CD4+ and CD8+T cells and their subsets as well as regulatory T cells (Treg) were studied. Detailed analyses on infections occurring after 3 months were also assessed. The 18-month cumulative incidences of infection-related death were 8 and 3%, and of infections were 72 and 57% after MMUD and UCB transplantation, respectively. Rates of infection per 12 patient-month were roughly 2 overall (1 for bacterial, 0.9 for viral and 0.3 for fungal infections). Memory, naïve CD4+ and CD8+T cells, naïve B cells and Treg cells reconstitution between the 2 sources was roughly similar. Absolute CD4+T cells hardly reached 500 per μL by one year posttransplantation and most B cells were of naïve phenotype. Correlations between immune reconstitution and infection were then performed by multivariate analyses. Low CD4+ and high CD8+T cells absolute counts at 3 months were linked to increased risks of overall and viral (but not bacterial) infections. When assessing for the naïve/memory phenotypes at 3 months among the CD4+ T cell compartment, higher percentages of memory subsets were protective against late infections: central memory CD4+T cells protected against overall and bacterial infections; late effector memory CD4+T cells protected against overall, bacterial and viral infections. At the opposite, high percentage of effector- and late effector-memory subsets at 3 months among the CD8+ T cell compartment predicted higher risks for viral infections. Patients transplanted from alternative donors represent a population with very high risk of infection. Detailed phenotypic analysis of immune reconstitution may help to evaluate infection risk and to adjust infection prophylaxis. [less ▲]

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See detailCXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation
Glauzy, Salomé; André-Schmutz, I; Larghero, J et al

in PLoS ONE (2014), 9(3), 91492

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