Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition

Fisher, Sheila; Cutler, Antony J.; Dorée, Carolyn; Brunskill, Susan J; Stanworth, Simon; Navarrete, Cristina; Girdlestone, John

doi:10.1002/14651858.cd009768.pub2

Cited by 72 publications

(74 citation statements)

References 68 publications

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“…Our meta-analysis indicates that the prophylactic administration of allogeneic MSC to patients undergoing HSCT increases the probability of survival, partly because MSC prevent the occurrence of GvHD. A recent meta-analysis [33] including five randomized controlled trials (RCTs) showed no significant differences for allcause mortality between MSC and no MSC groups, in contrast to our results. We believed that these different results could be due to the lower number of cases and shorter end point of this study.…”

Section: Discussioncontrasting

confidence: 99%

“…The characteristics of the 35 studies reporting data for the treatment of aGvHD and/or cGvHD are summarized in Table S3 (see Additional file, pp. [33][34][35][36]. Only six of these studies reported data of interest for control patients (aGvHD, n = 182 patients; cGvHD, n = 14 patients; Table S4, pp.…”

Section: Mesenchymal Stromal Cells For the Treatment Of Steroidrefracmentioning

confidence: 99%

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Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

et al. 2020

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Background: Graft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed for the prevention and the treatment of GvHD in patients undergoing HSCT. Unfortunately, previous studies reported conflicting results regarding the prophylactic and therapeutic effects of MSC for GvHD. Consequently, we carried out a meta-analysis to clarify whether MSC administration can improve the dismal outcome of these patients. Methods:We carried out a systematic review and selected studies (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019) reporting data about the administration of allogeneic MSC for the prevention (n = 654 patients) or treatment of acute (n = 943 patients) or chronic (n = 76 patients) GvHD after HSCT. Our primary outcome was overall survival at the last follow-up. The secondary outcomes were the response and development of GvHD. Subgroup analyses included age, MSC dose, first infusion day after HSCT, number of organs and organ-specific involvement, acute GvHD grade (I-IV), and chronic GvHD grade (limited or extensive).Results: Patients infused with MSC for GvHD prophylaxis showed a 17% increased overall survival (95% CI, 1.02-1.33) and a reduced incidence of acute GvHD grade IV (RR = 0.22; 95% CI, 0.06-0.81) and chronic GvHD (RR = 0.64; 95% CI, 0.47-0.88) compared with controls. Overall survival of acute GvHD patients (0.50; 95% CI, 0.41-0.59) was positively correlated with MSC dose (P = 0.0214). The overall response was achieved in 67% (95% CI, 0.61-0.74) and was complete in 39% (95% CI, 0.31-0.48) of acute patients. Organ-specific response was higher for the skin. Twentytwo percent (95% CI, 0.16-0.29) of acute patients infused with MSC developed chronic GvHD. Sixty-four percent (95% CI, 0.47-0.80) of chronic patients infused with MSC survived; the overall response was 66% (95% CI, 0.55-0.76) and was complete in 23% (95% CI 0.12-0.34) of patients. Conclusions:Our meta-analysis indicates that allogeneic MSC could be instrumental for the prophylaxis and treatment of GvHD. Future trials should investigate the effect of the administration of MSC as an adjuvant therapy for the treatment of patients with GvHD from the onset of the disease.

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Section: Discussioncontrasting

confidence: 99%

Section: Mesenchymal Stromal Cells For the Treatment Of Steroidrefracmentioning

confidence: 99%

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

et al. 2020

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“…A number of studies have assessed the safety and efficacy of cell therapies in adults with GVHD, as described in the recent meta-analysis [39]. A number of factors are relevant to the experience reported in adults with aGVHD treated with MSCs, including variations in the type of design (prophylaxis versus treatment of GVHD), type of MSCs (adipose tissue, cord blood, or bone marrow derived cells), specific trial design elements (first line in new-onset GVHD, concomitant corticosteroids and MSCs after GVHD diagnosis, or established steroid refractory), choice of primary efficacy endpoint (the currently established day 28 overall response or durable complete response), choice or comparator, and specific aGVHD patient attributes such as severity of disease and organ involvement.…”

Section: Discussionmentioning

confidence: 99%

A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease

Kurtzberg

Abdel‐Azim

Carpenter

et al. 2020

Biology of Blood and Marrow Transplantation

108

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Steroid-refractory acute graft-versus-host disease (SR-aGVHD) following hematopoietic cell transplantation (HSCT) is associated with poor clinical outcomes. Currently, there are no safe and effective therapies approved for use in the pediatric population under the age of 12 years. Accordingly, there is an urgent need for new treatments that are safe, well tolerated, and effective in managing this debilitating and potentially fatal complication of HSCT. In early phase clinical trials, mesenchymal stromal cells (MSCs) have demonstrated efficacy in the treatment of acute GVHD (aGVHD) in pediatric patients. We now report the results of a phase 3, prospective, single-arm, multicenter study (NCT02336230) in 54 children with primary SR-aGVHD who were naive to other immunosuppressant therapies for aGVHD treated with MSC product (remestemcel-L) dosed at 2 £ 10 6 cells/kg twice weekly for 4 weeks. Remestemcel-L therapy significantly improved day 28 overall response rate (OR) compared with the prespecified control OR value of 45% (70.4% versus 45%, P = .0003). The statistically significant OR (70.4%) was sustained through day 100, including an increase in complete response from 29.6% at day 28 to 44.4% at day 100. Overall survival was 74.1% at day 100 and 68.5% at day 180. Overall response in all participants at day 28 was highly predictive of improved survival through 180 days, and survival was significantly greater in day 28 responders compared with nonresponders through day 100 (86.8% versus 47.1% for responders and nonresponders, respectively, P = .0001) and through day 180 (78.9% versus 43.8%, P = .003). Remestemcel-L was well tolerated with no identified infusion-related toxicities or other safety concerns. This study provides robust, prospective evidence of the safety, tolerability, and efficacy of remestemcel-L as first-line therapy after initial steroid failure in pediatric SR-aGVHD.

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“…В дополнение к их способности к дифференцировке в различные клеточные линии МСК обладают иммуносупрессивными свойствами [18,19], секретируя большое число растворимых факторов, таких как индолеамин-2,3-диоксеназа (IDO), простагландин-2, интерлейкин (ИЛ)-10, трансформирующий фактор роста β, оксид азота, HLA-G5, белок-индуцибельный фактор-индуцируемый опухолевым геном 6 (TSG-6), МСК способны ингибировать активацию комплемента, подавлять пролиферацию Т-и В-лимфоцитов, NK-клеток, менять соотношение между различными субпопуляциями Т-клеток, индуцировать пролиферацию регуляторных Т-клеток. Вследствие этого МСК используют для лечения различных заболеваний: болезнь Крона, болезнь Альцгеймера, инфаркт миокарда, сахарный диабет 1-го типа [11,[21][22][23].…”

Section: ââåäåíèåunclassified

Multipotent mesenchymal stromal cells application for acute graft versus host disease treatment

Кузьмина¹,

Petinati²,

Vasilieva³

et al. 2020

Terapevticheskii arkhiv

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Aim.Analysis of the effectiveness of the MSCs aministration as the second- or third-line therapy of acute GVHD (aGVHD) resistant to glucocorticosteroid treatment. Materials and methods.The study included 35 patients who received MSCs obtained from the bone marrow of healthy donors as a treatment of steroid-resistant aGVHD. The clinical parameters of patients, MSCs cultural characteristics, the MSC expression profile for various genes including those involved in immunomodulation, expression of cells surface markers, the source of MSCs, as well as the frequency and number of MSC administrations were analyzed. Results.Response to therapy was achieved in 74% of cases, a complete response was reached in 13 (37%) patients, partial response/clinical improvement was demonstrated in 13 (37%). This treatment was ineffective in 9 patients. The prediction of a group of patients with good response to MSC therapy turned to be impossible. The differences between the effective and ineffective for the GVHD treatment MSCs samples were found. The effective ones were characterized with a decreased total MSCs production and an increase in the main histocompatibility complex and PDL-1 antigens expression. Conclusion.These data allow to select optimal samples for aGVHD treatment that can improve clinical results. aGVHD treatment with MSCs has shown efficacy comparable to other treatment approaches. Given the low percentage of complications and the absence of significant adverse effects, MSC therapy seems to be one of the optimal approaches to the treatment of resistant forms of GVHD.

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Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition

Abstract: Mesenchymal stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant (HSCT) recipients with a haematological condition.

Cited by 72 publications

References 68 publications

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

A Phase 3, Single-Arm, Prospective Study of Remestemcel-L, Ex Vivo Culture-Expanded Adult Human Mesenchymal Stromal Cells for the Treatment of Pediatric Patients Who Failed to Respond to Steroid Treatment for Acute Graft-versus-Host Disease

Multipotent mesenchymal stromal cells application for acute graft versus host disease treatment

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