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Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease.

ABSTRACT: Acute graft-versus-host disease (aGvHD) continues to impact morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). First-line therapy for aGvHD still remains the use of high-dose corticosteroids. Unfortunately, 40-60% of patients with aGvHD exhibit steroid resistance, which is associated with a very poor prognosis. As no effective second-line therapy existed, in recent decades various treatment options were considered for the treatment of therapy-refractory GvHD. Based on their in vitro immunomodulatory properties, the use of mesenchymal stromal cells (MSCs) in the treatment of aGvHD has been introduced. However, most of the clinical data are generated from uncontrolled trials and case series, showing clinical responses to MSCs. Clinical results are more consistent in children despite the use of MSC preparations of various provenance and manufacturing protocols. While these data support the therapeutic principle, the great variability of outcomes strongly suggests that not all MSC preparations are equal and that the specific manufacturing protocols influence therapeutic success in vivo.

SUBMITTER: Elgaz S

PROVIDER: S-EPMC6558336 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease.

Elgaz Sümeyye S Kuçi Zyrafete Z Kuçi Selim S Bönig Halvard H Bader Peter P

Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie 20190204 1

Acute graft-versus-host disease (aGvHD) continues to impact morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). First-line therapy for aGvHD still remains the use of high-dose corticosteroids. Unfortunately, 40-60% of patients with aGvHD exhibit steroid resistance, which is associated with a very poor prognosis. As no effective second-line therapy existed, in recent decades various treatment options were considered for the treatment of therapy-refractory GvHD. Based on ...[more]

PMID: 31244579

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Project description:BackgroundGraft-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.MethodsWe carried out a systematic review and selected studies (2004-2019) 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).ResultsPatients 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. Twenty-two 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.ConclusionsOur 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.

Dataset Information

Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease.

Publications

Clinical Use of Mesenchymal Stromal Cells in the Treatment of Acute Graft-versus-Host Disease.

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