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Objective To evaluate extent of interstitial lung disease (ILD) and oesophageal involvement using high-resolution computed tomography (HRCT) in early diffuse SSc patients after autologous haematopoietic stem cell transplantation (aHSCT). Methods Overall chest HRCT, lung function and skin score changes were evaluated in 33 consecutive diffuse SSc patients before and after aHSCT during yearly routine follow-up visits between January 2000 and September 2016. Two independent radiologists blindly assessed the ILD extent using semi-quantitative Goh and Wells method, the widest oesophageal diameter (WOD) and the oesophageal volume (OV) on HRCT. Patients were retrospectively classified as radiological responders or non-responders, based on achieved stability or a decrease of 5% or more of HRCT-ILD at 24 months post-aHSCT. Results Using a linear mixed model, the regressions of the extent of ILD and of ground glass opacities were significant at 12 months (ILD P  = 0.001; ground glass opacities P  = 0.0001) and at 24 months (ILD P  = 0.007; ground glass opacities P  = 0.0008) after aHSCT, with 18 patients classified as radiological responders (probability of response 0.78 [95% CI 0.58, 0.90]). Meanwhile the WOD and the OV increased significantly at 12 months (WOD P  = 0.03; OV P  = 0.34) and at 24 months (WOD P  = 0.002; OV P  = 0.007). Kaplan–Meier analyses showed a trend towards better 5-year survival rates (100% vs 60%; hazard ratio 0.23 [95% CI 0.03, 1.62], P  = 0.11) among radiological responders vs non-responders at 24 month follow-up after aHSCT. Conclusion Real-world data analysis confirmed significant improvement in extent of HRCT SSc-ILD 24 months after aHSCT, although oesophageal dilatation worsened requiring specific attention. [ABSTRACT FROM AUTHOR]

Objective: To quantify the magnitude, domains, and duration of change in health‐related quality of life (HRQoL) in patients with systemic sclerosis (SSc) who underwent autologous hematopoietic stem cell transplantation (HSCT) as compared to SSc patients with similar characteristics who did not undergo autologous HSCT. Methods: The study was designed as a retrospective study comparing SSc patients who underwent autologous HSCT and SSc patients who met the criteria for transplantation but were treated with conventional care. Outcomes included scores on the 36‐item Short Form (SF‐36) health survey and the Health Assessment Questionnaire (HAQ) and its disease‐specific symptom scales. Differences in scores between the groups were compared using linear models, adjusting for baseline scores and inverse probability of treatment and censoring weights. Results: In total, 41 SSc patients who underwent autologous HSCT and 65 SSc patients treated with conventional care were compared. In marginal linear weighted models, the SF‐36 physical component summary score was a mean ± SEM 7.02 ± 1.94 points higher at the first annual visit (P = 0.001) and 14.40 ± 6.16 points higher at the seventh annual visit (P = 0.03) in patients treated with autologous HSCT compared to the conventional care group. HAQ scores were significantly better in the autologous HSCT group compared to the conventional care group during follow‐up (mean ± SEM difference from baseline −0.57 ± 0.13 [P < 0.001] at the first annual visit and −0.94 ± 0.49 [P = 0.07] at the seventh annual visit). There were no differences in the SF‐36 mental component summary scores between the 2 groups either at baseline or during follow‐up. Conclusion: This study provides robust complementary HRQoL data, including overall and event‐free survival data, to expand on the standard repertoire of biomedical variables, thus potentially supporting the physical benefits of autologous HSCT in patients with SSc. [ABSTRACT FROM AUTHOR]

Objectives In severe rapidly progressive SSc, autologous haematopoietic stem cell transplantation (AHSCT) allows significant improvements in overall and event-free survival. We undertook this study to identify, appraise and synthesize the evidence on health-related quality of life (HRQoL) before and after AHSCT for SSc. Methods We performed a systematic review of the literature, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed and ScienceDirect from database inception to 1 February 2019. All articles with original HRQoL data were selected. Results The search identified 1080 articles, of which 8 were selected: 3 unblinded randomized controlled trials [American Scleroderma Stem Cell versus Immune Suppression Trial (ASSIST), Autologous Stem Cell Transplantation International Scleroderma, Scleroderma: Cyclophosphamide or Transplantation), 3 uncontrolled phase I or II trials and 2 cohort studies. HRQoL data from 289 SSc patients treated with AHSCT and 125 treated with intravenous CYC as a comparator with median 1.25–4.5 years follow-up were included. HRQoL was evaluated with the HAQ Disability Index (HAQ-DI; 275 patients), the 36-item Short Form Health Survey (SF-36; 249 patients) and the European Quality of Life 5-Dimensions questionnaire (EQ-5D; 138 patients). The quality of the studies was moderate to low. AHSCT was associated with significant improvement in the HAQ-DI (P = 0.02–<0.001), SF-36 Physical Component Summary score (P = 0.02–<0.0001) and EQ-5D index-based utility score (P < 0.001). The SF-36 Mental Component Summary score improved in the ASSIST (n = 19) and one small retrospective cohort (n = 30 patients, P = 0.005) but did not improve significantly in 2 randomized controlled trials (n = 200 patients, P = 0.1–0.91). Conclusion AHSCT in severe SSc patients is associated with significant and durable improvement in physical HRQoL. [ABSTRACT FROM AUTHOR]

Background: Patients with systemic lupus erythematosus (SLE) with inadequate responses to standard therapies have unmet therapeutic needs. The immunomodulatory, proangiogenic, and antifibrotic properties of mesenchymal stromal cells support their use in treating patients with SLE. We aimed to assess the safety of a single intravenous infusion of allogeneic umbilical cord-derived mesenchymal stromal cells in patients with severe SLE., Methods: This prospective, single-centre, open-label, dose-escalation, Bayesian phase 1 study was done at the Saint-Louis University Hospital (Paris, France). Eligible patients were aged 18-70 years, were diagnosed with SLE according to American College of Rheumatology criteria with positive antinuclear antibodies, had a baseline Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score of 6 or more, and had disease that was refractory to first and second line SLE therapies. Patients were to receive a single intravenous infusion of 1 × 10 6 , 2 × 10 6 , or 4 × 10 6 umbilical cord-derived mesenchymal stromal cells per kg (manufactured from a single umbilical cord) in cohorts of five patients per dose, starting at 2 × 10 6 cells per kg. The primary endpoint was the rate of treatment-related severe adverse events (grade ≥3) in the first 10 days after infusion of umbilical cord-derived mesenchymal stromal cells. People with lived experience were involved in study design, patient enrolment, and dissemination of the study findings. This study is registered with ClinicalTrials.gov, NCT03562065, and the EU Clinical Trials Register, EudraCT2017-001400-29., Findings: From May 14, 2019, to March 6, 2023, 29 patients were screened for eligibility, eight of whom were enrolled in the study. Enrolment was terminated early after inclusion of eight patients and no patients received the 1 × 10 6 dose of umbilical cord-derived mesenchymal stromal cells. Seven (88%) of eight participants were cisgender women and one (13%) was a cisgender man. The median age was 35 years (range 26-57) and the median SLE disease duration was 12 years (5-19). All patients received at least 2 × 10 6 cells per kg (range 2 × 10 6 to 4 × 10 6 ). No severe adverse events and three infusion-related adverse events (two grade 1 and one grade 2) occurred in two patients in the first 10 days after infusion. After 12·4 months (range 12-13) of follow-up, no treatment-related severe adverse events and three non-treatment-related severe adverse events occurred in one patient after relapse., Interpretation: Our results suggest that a single infusion of 2 × 10 6 cells per kg or 4 × 10 6 cells per kg of allogeneic umbilical cord-derived mesenchymal stromal cells was safe in patients with severe SLE. Placebo-controlled trials are needed to confirm clinical efficacy and the role of B-cell modifications in clinical benefit., Funding: Fondation du Rein, Alliance Maladies Rares AFM-Téléthon, Direction de la Recherche Clinique et de l'Innovation AP-HP, and ANR eCellFrance., Competing Interests: Declaration of interests MWL is co-founder and part-time chief scientific officer of INmune Bio, a biotech company that holds intellectual property surrounding an alternative umbilical cord-derived mesenchymal stromal cell product, which was not used in this trial. BW is employed part-time by INmune Bio and holds intellectual property surrounding an alternative umbilical cord-derived mesenchymal stromal cell product through University College London (London, UK). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Contribution of mesenchymal stromal cell transplantation in systemic scleroderma Systemic scleroderma is a rare chronic autoimmune disease with the highest mortality rate among rheumatologic diseases. Its pathophysiology is based on three mechanisms: endothelial damage with initial vasculopathy, activation of the immune response, progressive fibrosis of the skin and various organs. Cellular therapy allows to envision new perspectives: autologous hematopoietic stem cell transplantation has been widely validated to treat severe forms of the disease, but its use is restricted to the most severely affected patients and contraindicated in advanced forms of the disease. The use of mesenchymal stromal cells, and their immunomodulatory, pro-angiogenic and anti-fibrotic properties, as well characterized in vitro and in vivo, broadens the field of possibilities. The use of mesenchymal stromal cells in targeted indications (treatment of graft versus host disease, crohn's disease fistulas, etc.) Has received market authorization and is currently being studied in systemic scleroderma with very promising results., Competing Interests: Les auteures déclarent n’avoir aucun lien d’intérêts.

Background: All the cellular partners of the vascular system and especially endothelial cells are involved in the pathophysiology of the vasoocclusive crises associated with sickle cell disease. In sickle cell disease, circulating cells adhere abnormally to endothelial cells in a chronic pro-inflammatory context. Hydroxycarbamide is the only drug with demonstrated efficacy to reduce the frequency of vasoocclusive crises. Here, we investigated the effects of hydroxycarbamide and/or cytokines on the expression of genes related to adhesion events in endothelial cells from three different vascular sites., Design and Methods: Endothelial cells representative of the macro- (HUVEC) or microcirculation (TrHBMEC and HPMEC) were grown in the presence or absence of hydroxycarbamide and/or cytokines (TNFα and IFNγ). Expression of genes encoding adhesion proteins was analyzed by RQ-PCR, ELISA, flow cytometry, in situ ELISA for extracellular matrix proteins, and Western blot., Results: In cells from the microcirculation, expression of TSP-1, vWF, and PECAM-1 genes was decreased by hydroxycarbamide and/or cytokine treatment at the mRNA level. In the macro-circulation their expression was unaffected or increased. Hydroxycarbamide significantly decreased vWF incorporated in the TrHBMEC extracellular matrix. CD36 mRNA was strongly down-regulated by cytokines in HPMEC, the only cell type in which it is expressed. Hydroxycarbamide decreased soluble PECAM-1 in HUVEC supernatants., Conclusions: Our results highlight the heterogeneity of vascular endothelial cell responses to hydroxycarbamide and/or cytokines depending upon their origin. They also suggest that hydroxycarbamide has an anti-adhesogenic effect on endothelial cells, but by mechanisms which could vary according to their macro- or microcirculation and organ origin.