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See detailInfusion of mesenchymal stromal cells after deceased liver transplantation: A phase I-II, open-label, clinical study.
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Journal of Hepatology (2017), 67(1), 47-55

BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the ... [more ▼]

BACKGROUND & AIM: Mesenchymal stromal cell (MSC) infusion could be a mean to establish tolerance in solid organ recipients. The aim of this prospective, controlled, phase-1 study was to evaluate the feasibility, safety and tolerability of a single infusion of MSCs in liver transplant recipients. METHODS: Ten liver transplant recipients under standard immunosuppression received 1.5-3x106/kg third-party unrelated MSCs on post-operative day 3+/-2, and were prospectively compared to a control group of 10 liver transplant recipients. As primary end-points, MSC infusional toxicity was evaluated, and infectious and cancerous complications were prospectively recorded until month 12 in both groups. As secondary end-points, rejection rate, month-6 graft biopsies, and peripheral blood lymphocyte phenotyping were compared. Progressive immunosuppression weaning was attempted from month 6 to 12 in MSC recipients. RESULTS: No variation in vital parameters or cytokine release syndrome could be detected during and after MSC infusion. No patient developed impairment of organ functions (including liver graft function) following MSC infusion. No increased rate of opportunistic infection or de novo cancer was detected. As secondary end-points, there was no difference in overall rates of rejection or graft survival. Month-6 biopsies did not demonstrate a difference between groups in the evaluation of rejection according to the Banff criteria, in the fibrosis score or in immunohistochemistry (including Tregs). No difference in peripheral blood lymphocyte typing could be detected. The immunosuppression weaning in MSC recipients was not successful. CONCLUSIONS: No side effect of MSC infusion at day 3 after liver transplant could be detected, but this infusion did not promote tolerance. This study opens the way for further MSC or Treg-based trials in liver transplant recipients. LAY SUMMARY: Therapy with mesenchymal stromal cells (MSCs) has been proposed as a mean to improve results of solid organ transplantation. One of the potential MSC role could be to induce tolerance after liver transplantation, i.e. allowing the cessation of several medications with severe side effects. This study is the first-in-man use of MSC therapy in 10 liver transplant recipients. This study did not show toxicity after a single MSC infusion but it was not sufficient to allow withdrawal of immunosuppression. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil; Bodart, Gwennaëlle ULg; RENARD, Jeanne de Chantal ULg et al

Poster (2017, May 23)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailA surprising and dramatic neuroendocrine-immune phenotype of mice deficient in Growth Hormone-Releasing Hormone (GHRH)
Farhat, Khalil ULg; Bodart, Gwennaëlle ULg; Renard, chantal et al

Poster (2017, May)

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a ... [more ▼]

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh-/- mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell responses of Ghrh-/- mice were not severely affected but a constant B-cell lymphopaenia was observed. Thus, we investigated vaccine and anti-infectious responses of Ghrh-/- mice toward Streptococcus pneumonia, a B-dependent pathogen, Ghrh-/- mice were unable to trigger production of specific IgM and IgG against serotype 1 pneumococcal polysaccharide (PPS) after vaccination with either native PPS (Pnx23) or protein-PPS conjugate (Prev-13) vaccines. These vaccines both include the serotype 1 (our S.pneumoniae strain) and provide an effective protection in mice. A short GH supplementation to Ghrh-/- mice (1 daily injection of 1 mg/kg GH for 4 weeks) restored IgM and IgG response to Pnx23 vaccine but not to Prev-13. This suggests that GH could exert distinct impacts upon spenic areas. Furthermore, after intranasal instillation of a non-lethal dose (defined by the full clearance by WT C57BL/6 mice after 24h) of serotype 1 S.pneumoniae, Ghrh-/- mice exhibited a dramatic susceptibility. This was proved by a marked time-dependent increase in pulmonary bacterial, a septicemia already 24h after infection and a survival limit of 72h. We also observed a dramatic decrease in lung B- and T-cell populations and an increase in proportion of inflammatory macrophages. By contrast, wild-type and heterozygote mice completely cleared S.pneumoniae infection after 24h. In conclusion, our data show without ambiguity that the somatotrope GHRH/GH/IGF-1 axis plays an important and unsuspected role in defense against S.Pneumoniae. [less ▲]

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See detailAzacytidine prevents experimental xenogeneic graft-versus-host disease without abrogating graft-versus-leukemia effects
Ehx, Grégory ULg; Fransolet, Gilles ULg; De Leval, Laurence et al

in Oncoimmunology (2017)

The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading ... [more ▼]

The demethylating agent 5-azacytidine (AZA) has proven its efficacy as treatment for myelodysplastic syndrome and acute myeloid leukemia. In addition, AZA can demethylate FOXP3 intron 1 (FOXP3i1) leading to the generation of regulatory T cells (Treg). Here, we investigated the impact of AZA on xenogeneic graft-versus-host disease (xGVHD) and graft-versus-leukemia effects in a humanized murine model of transplantation (human PBMCs-infused NSG mice), and described the impact of the drug on human T cells in vivo. We observed that AZA improved both survival and xGVHD scores. Further, AZA significantly decreased human T-cell proliferation as well as IFN-γ and TNF-α serum levels, and reduced the expression of GRANZYME B and PERFORIN 1 by cytotoxic T cells. In addition, AZA significantly increased Treg frequency through hypomethylation of FOXP3i1 as well as increased Treg proliferation. The later was subsequent to higher STAT5 signaling in Treg from AZA-treated mice, which resulted from higher IL-2 secretion by conventional T cells from AZA-treated mice itself secondary to demethylation of the IL-2 gene promoter by AZA. Importantly, Tregs harvested from AZA-treated mice were suppressive and stable over time since they persisted at high frequency in secondary transplant experiments. Finally, graft-versus-leukemia effects (assessed by growth inhibition of THP-1 cells, transfected to express the luciferase gene) were not abrogated by AZA. In summary, our data demonstrate that AZA prevents xGVHD without abrogating graft-versus-leukemia effects. These findings could serve of basis for further studies of GVHD prevention by AZA in acute myeloid leukemia patients offered an allogeneic transplantation. [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 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

Conference (2017, March 16)

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3 ... [more ▼]

Mesenchymal stromal cells (MSC)-based therapy has been proposed in kidney transplantation (KTx). We report on the 1-year follow-up of an open-label phase I trial using MSC in KTx. On postoperative day 3, third-party MSC (~2.0x106/kg) were administered to 7 non-immunized first-transplant recip- ients from deceased donors, under standard immunosuppression (Basiliximab, Tacrolimus, MMF and steroids). No HLA matching was required for MSC donors. Seven comparable KTx recipients were included as controls. Informed consent was obtained. No 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. Ten months after KTx, 1 MSC patient had type B aortic dissection and STEMI. Four MSC patients had at least 1 opportunistic infection, whereas 3 controls had polyoma-BK viremia. At day 14, 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 46.5 ± 18.6 and 54.2 ± 16.3 ml/min, respectively (p, 0.42). Per-cause biopsies evidenced 1 bor- derline and 1 acute rejections in MSC group, whereas no AR was biopsy-proven in controls. Three patients developed anti-HLA antibodies against MSC (n=1) or shared kidney/MSC (n=2) mismatches.MSC infusion was safe in all patients except one. Incidence of opportunist infections was similar in both groups. 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 detailImmunomodulatory effects of rapamycin in xenogeneic Graft versus Host Disease
Ehx, Grégory ULg; Hannon, Muriel ULg; DUBOIS, Sophie ULg et al

in Biology of Blood and Marrow Transplantation (2017, March), 23(3), 365366

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Several studies have suggested that rapamycin (RAPA), an mTOR ... [more ▼]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Several studies have suggested that rapamycin (RAPA), an mTOR inhibitor with immunosuppressive properties, may reduce GVHD severity and mortality, possibly by promoting regulatory T cells (Tregs). However, few data have been reported about the impact of this drug on overall T cell population. The present work aims at investigating the mechanisms by which RAPA impacts GVHD in a humanized mouse model of GVHD (NSG mice infused with human PBMCs). We observed that RAPA injections significantly reduced xenogeneic GVHD lethality and severity. RAPA dramatically reduced human cells chimerism in RAPA mice and increased CD4+/CD8+ T cells balance due to a lower proliferation of CD8+ T cells. In addition, the frequencies of naive CD4+ and CD8+ T cells were higher and the CD4+ T cells showed a reduced effector phenotype (CD45RO+CD27-). Further, the differentiation of helper T cells (Th1, Th2 and Th17) was significantly decreased in treated mice. Tregs were positively affected as RAPA up-regulated their expression of BCL-2 and KI67 as well as their STAT5 phosphorylation level, leading to higher Treg frequency in treated mice. Altogether these data suggest that RAPA ameliorates GVHD by lowering cytotoxic and effector CD4+ T cells frequency as well as promoting Tregs. [less ▲]

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See detailUNE INJECTION UNIQUE DE CELLULES STROMALES MESENCHYMATEUSES AU JOUR 3 APRES GREFFE HEPATIQUE EST INSUFFISANTE POUR INDUIRE UNE TOLERANCE OPERATIONNELLE
DETRY, Olivier ULg; VANDERMEULEN, Morgan ULg; DELBOUILLE, Marie-Hélène ULg et al

in Transplant International (2017, January), 30(suppl 1), 812

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis ... [more ▼]

Introduction: Mesenchymal stromal cell (MSC) infusion could be a mean to establish donor-specific immunological tolerance in solid organ recipients. The aim of this phase 2 study was test the hypothesis of possible induction of operative tolerance by third-party MSC in liver transplant (LT) recipients. Methods: 10 stable and low-risk LT recipients under standard immunosup- pression (Tac-MMF- low dose steroids) received 1.5–3 9 106/kg third-party MSCs on post-operative day 3 ` 2. By protocol, progressive weaning of immunosuppression was attempted in patients who did not develop rejection and had normal graft function and month-6 graft biopsy. Tacrolimus was progressively tapered from day 180 to be discontinued by day 270. After day- 270 graft biopsy, MMF was progressively tapered and definitely discontinued by day 365 in the absence of rejection. Results: One patient from the MSC group was excluded from immunosup- pression withdrawal attempt due to HCC recurrence, and the 9 others met the necessary criteria. In one patient, tacrolimus and MMF withdrawal was performed without rejection. In two patients, MMF monotherapy was achieved at month 9, but graft rejection occurred during MMF withdrawal and was successfully treated by tacrolimus reintroduction. In 6 patients, the transam- inases significantly increased during tacrolimus withdrawal. In these cases, withdrawal was cancelled and liver tests normalised after increase of the tacrolimus dose. No graft was lost due to the withdrawal attempt. Conclusion: A single post transplant MSC injection is not sufficient to induce operative tolerance after LT. [less ▲]

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See detailOutcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Roux, C; Tifratene, K; Socié, G et al

in Bone Marrow Transplantation (2017), 52

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent ten-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted in chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and DLI (n=30), or isolated reinfusion of donor lymphocytes (DLI) (n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy = 385 d, second allograft = 391d, chemotherapy = 174d, DLI alone = 140d, palliative care = 43d. A second SCT or a combination of chemotherapy and donor lymphocytes infusion yielded similar outcome (HR=0.85, p=0.53) unlike chemotherapy alone (HR 1.43 p=0.04), palliative care (HR=4.24, p<0.0001) or isolated DLI (HR=1,94, p<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML. [less ▲]

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See detailReduced intensity and non-myeloablative allogenic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin's lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy
Gauthier, J; Castagna, L; Garnier, F et al

in Bone Marrow Transplantation (2017), 52

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed ... [more ▼]

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N = 34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N = 31, 91%) or a RIC (N = 3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR) = 2.02, P = 0.03 and HR = 2.43, P = 0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with posttransplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting. [less ▲]

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See detailMultiple myeloma bone disease: from mechanisms to next generation therapy
Heusschen, Roy ULg; Muller, Joséphine ULg; WITHOFS, Nadia ULg et al

in Belgian Journal of Hematology (2017), 8

Multiple myeloma bone disease is a major cause of morbidity and mortality in multiple myeloma patients and persists even in patients in remission. Multiple myeloma bone disease is caused by an uncoupling ... [more ▼]

Multiple myeloma bone disease is a major cause of morbidity and mortality in multiple myeloma patients and persists even in patients in remission. Multiple myeloma bone disease is caused by an uncoupling of bone remodelling, with increased osteoclast activity and decreased osteoblast activity, culminating in lytic bone destruction. Bisphosphonates are the current standard-of-care but new therapies are needed. As the molecular mechanisms controlling multiple myeloma bone disease are increasingly understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds show promising results. In this review, we provide a comprehensive overview of the biology of multiple myeloma bone disease, summarise its current clinical management and discuss preclinical and clinical data on next generation therapies. [less ▲]

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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. (2017), 11

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 detailThe clinical relevance of imatinib plasma trough concentrations in chronic myeloid leukemia. A Belgian study
Van Obbergh, F; Knoops, L; Devos, T et al

in Clinical Biochemistry (2017), 50

This retrospectivemulticenter study in patientswith chronic myeloid leukemia in chronic phasewas undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice ... [more ▼]

This retrospectivemulticenter study in patientswith chronic myeloid leukemia in chronic phasewas undertaken to confirm the clinical relevance of imatinib plasma concentrations monitoring in daily practice. Forty-one patients, with 47 imatinib plasma measurements, were analyzed during treatment with imatinib given at a fixed 400mg daily dose. A significant inverse relationship of imatinib concentration with the patients' weight was observed (Pearson's test: p=0.02,R2=0.1). More interestingly, patientswith poor response (switched to another tyrosine kinase inhibitor because of imatinib failure, or because of disease progression after an initial response) displayed a significantly lower mean imatinib concentration as compared to patients maintained on imatinib (822 ng/mL vs 1099 ng/mL; Student's t-test, p=0.04). Failure or disease progression occurred more often in patients in the lowest quartile of imatinib concentrations compared to patients in the highest quartile (p = 0.02, logrank test). No correlation could be established with other biological or clinical parameter, including complete cytogenic response and majormolecular response. In conclusion: in patients treatedwith imatinib at a fixed daily dose of 400 mg, imatinib plasma concentrations decreased with increasing body weight and were lower in patients switched to another tyrosine kinase inhibitor due to imatinib failure. Systematic determination of imatinib plasma trough levels should be encouraged in such patients. [less ▲]

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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 Application of Mesenchymal Cells (2017)

Organ transplantation is the only definitive treatment for many critical diseases of the liver, kidney, heart, pancreas, and lungs. Although it is the primary therapeutic option at present, transplanted ... [more ▼]

Organ transplantation is the only definitive treatment for many critical diseases of the liver, kidney, heart, pancreas, and lungs. Although it is the primary therapeutic option at present, transplanted patients have to deal with the numerous side effects of life-long dependence on immunosuppressive drugs, and these drugs still fail to prevent chronic rejection of the transplanted organ in many cases. The risk of developing cancer and opportunistic infections is also markedly increased in solid organ transplant (SOT) recipients receiving long-term immunosuppressive therapy. Cancer and opportunistic infections cannot be completely avoided since they result from the immunosuppressive drugs used posttransplant that affect not only the anti-graft response but also the entire immune response. Finding a way to establish donor-specific immunological tolerance without the need for nonspecific immunosuppression remains one of the major goals in transplantation medicine [1,2]. Another important aim is the improvement of graft survival and function. Overall, graft survival is about 15 years, but the increasing shortage of organs has led to the use of expanded criteria for donor organs often donated by older individuals, which are less robust organs than those donated by younger donors. Mesenchymal stromal cell (MSCs) are currently being evaluated in SOT with the hope of achieving more selective immunosuppression, better graft function, and longer graft survival. [less ▲]

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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 Application of Mesenchymal Cells (2017)

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See detailReconstitution of adaptive immunity after umbilical cord blood transplantation and clinical implication regarding risk of infections
SERVAIS, Sophie ULg; Hannon, Muriel ULg; Peffault de Latour, R. et al

in Stem Cell Invest. (2017), 4

In comparison with allogeneic stem cell transplantation (alloHSCT) with other stem cell sources, umbilical cord blood transplantation (UCBT) was traditionally associated with increased risk of infections ... [more ▼]

In comparison with allogeneic stem cell transplantation (alloHSCT) with other stem cell sources, umbilical cord blood transplantation (UCBT) was traditionally associated with increased risk of infections, particularly during the first 3 months after transplantation. Longitudinal studies of immune monitoring reported peculiar patterns of T- and B-cell recovery in the peripheral blood of UCB recipients during the first months post-transplantation. Overall, current data suggest delayed reconstitution of naive and memory CD4+ and CD8+ T-cell pools after UCBT. This is particularly true for adult recipients and for patients who received in vivo T-cell depleting approaches before the transplantation. Such delayed T-cell recovery may increase susceptibility of UCB recipients for developing opportunistic infections and viral reactivations. Regarding B-cell recovery, UCBT was associated with accelerated B-lymphopoiesis. Recent studies also reported evidence for faster functional memory B-cell recovery in UCB recipients. In this article, we briefly review T- and B-cell reconstitution after alloHSCT, with emphasis on peculiarities observed after UCBT. We further put these data in lines with risks of infections after UCBT. [less ▲]

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See detailMesenchymal stromal cell therapy for inflmmatory bowel diseases
GREGOIRE, Céline ULg; LECHANTEUR, Chantal ULg; BRIQUET, Alexandra ULg et al

in Alimentary Pharmacology & Therapeutics (2017), 45

Background Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells ... [more ▼]

Background Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro-inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair. Aim To review the current data on mesenchymal stromal cell therapy in IBD. Method We searched PubMed and ‘ClinicalTrials.gov’ databases using the terms ‘mesenchymal stromal cells’, ‘mesenchymal stem cell transplantation’, ‘inflammatory bowel diseases’, ‘Crohn disease’ and ‘colitis, ulcerative’. Additional publications were identified from individual article reference lists. Results MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen-presenting cells into a regulatorylike profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn’s disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission. Conclusions Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn’s disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials. [less ▲]

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