Prognostic value of CPSS cytogenetic risk classification in patients with CMML after allogeneic hematopoietic cell transplantation : a retrospective multicenter study of the Chronic Malignancies Working Party of the EBMT

Non peer reviewe

Use of human mesenchymal cells to improve vascularization in a mouse model for scaffold-based dermal regeneration

All engineered bioartificial structures developed for tissue regeneration require oxygen and nutrients to establish proper physiological functions. Aiming to improve vascularization during dermal regeneration, we combined the use of a bioartificial collagen scaffold and a defined human mesenchymal cell (MC) line. This cell line, termed V54/2, exhibits typical morphologic and immunohistochemical characteristics of MC. V54/2 cells seeded in the scaffold were able to survive, proliferate, and secrete significant amounts of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) during 2 weeks in vitro. To induce dermal regeneration, scaffolds with or without cells were transplanted in a nude mice full skin defect model. After 2 weeks of transplantation, scaffolds seeded with V54/2 cells showed more vascularization during the dermal regeneration process than controls, and the presence of human cells in the regenerating tissue was detected by immunohistochemistry. To confirm if local presence of angiogenic growth factors is sufficient to induce neovascularization, scaffolds were loaded with VEGF and bFGF and used to induce dermal regeneration in vivo. Results showed that scaffolds supplemented with growth factors were significantly more vascularized than control scaffolds (scaffolds without growth factors). The present work suggests that combined use of MC and bioartificial scaffolds induces therapeutic angiogenesis during the scaffold-based dermal regeneration process

Dissociation of osteogenic and immunological effects by the selective glucocorticoid receptor agonist, compound A, in human bone marrow stromal cells

Glucocorticoids (GCs) regulate various physiological processes, including bone remodeling. Whereas physiological amounts of GCs are required for proper human osteoblast differentiation, prolonged exposure to GCs leads to substantial bone loss in vivo predominantly by inhibiting osteoblast functions. Compound A (CpdA) is a novel GC receptor modulator with the potential of an improved benefit/risk profile. Here we tested the osteoimmunological effects of CpdA on primary human osteoblasts and their paracrine interactions with osteoclasts. To assess the anti-inflammatory potential of CpdA in human bone marrow stromal cell (BMSC)-derived osteoblasts, cells were stimulated with lipopolysaccharide and cytokine expression was determined. Similar to dexamethasone (DEX), CpdA profoundly suppressed lipopolysaccharide-induced TNF-alpha (-63%), IL-1 beta (-38%), and IL-6 (-36%) (P < 0.05) mRNA levels. Of note, CpdA failed to induce osteogenic differentiation of BMSCs, whereas DEX and budesonide enhanced matrix mineralization an d increased runt-related transcription factor 2 and alkaline phosphatase mRNA levels up to 5-fold in a dose-dependent manner. Interestingly, each substancepromotedcell proliferation by 7-10% and suppressed apoptosis by 25-30% at low concentrations and early differentiation stages, whereas high concentrations (1 mu M) suppressed proliferation and stimulated apoptosis in mature osteoblasts. Finally, CpdA did not increase the receptor activator of nuclear factor-kappa B ligand to osteoprotegerin mRNA ratio as compared with DEX and did not stimulate the formation of osteoclasts in coculture with BMSCs. In summary, CpdA displays dissociated osteogenic and immunological effects in human BMSCs that are distinct from those of conventional GCs. Whether the specific osteoimmunological profile of CpdA translates into a relevant in vivo effect needs to be further explored. (Endocrinology 152: 103-112, 2011

Impact of anti-thymocyte globulin on results of allogeneic peripheral blood stem cell transplantation for patients with Philadelphia-positive acute lymphoblastic leukaemia : An analysis by the Acute Leukemia Working Party of the EBMT

Background: Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). Methods: In the analysis, 1170 adult patients undergoing alloPBSCT from human leucocyte antigen-matched sibling or unrelated donors in the first complete remission between 2007 and 2016 were included. ATG was used in 429/575 (75%) and 121/595 (20%) patients transplanted from unrelated or sibling donors, respectively. Results: The incidence of chronic GVHD was 35% for patients treated with ATG compared with 52% in those not receiving ATG (p <0.001), while the rate of extensive chronic GVHD was 16% and 36%, respectively (p <0.001). The probability of survival free from GVHD and relapse (GRFS) was 42% and 32%, respectively (p = 0.002). In a multivariate model, the use of ATG was associated with reduced risk of overall chronic GVHD (hazard ratio [HR] = 0.52, p <0.001) and extensive chronic GVHD (HR = 0.46, p <0.001). It was also associated with better GRFS (HR = 0.77, p = 0.007), despite increased risk of relapse (HR = 1.41, p = 0.02). No significant effect was found with regard to the risk of non-relapse mortality and overall mortality. Conclusions: The use of ATG for patients with Ph+ ALL undergoing alloPBSCT is associated with reduced risk of chronic GVHD without impact on survival and therefore, could be considered. However, increased risk of relapse suggests the need for strict monitoring of minimal residual diseases and appropriate interventions after transplantation. (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe