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Review
. 2021 Aug 19:12:724380.
doi: 10.3389/fimmu.2021.724380. eCollection 2021.

Treatment of Steroid-Refractory Acute Graft- Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products

Makoto Murata  1 , Takanori Teshima  2
Affiliations
Review

Treatment of Steroid-Refractory Acute Graft- Versus-Host Disease Using Commercial Mesenchymal Stem Cell Products

Makoto Murata et al. Front Immunol. .

Abstract

Acute graft-versus-host disease (GVHD) is a life-threatening complication that can develop after allogeneic hematopoietic stem cell transplantation. In particular, the prognosis of patients with steroid-refractory acute GVHD is extremely poor. Ryoncil™ (remestemcel-L), a human bone marrow-derived mesenchymal stem cell (MSC) product, failed to show superiority over placebo in patients with steroid-refractory acute GVHD, but it was approved for use in pediatric patients in Canada and New Zealand based on the results of a subgroup analysis. Temcell®, an equivalent manufactured MSC product to remestemcel-L, was approved in Japan based on small single-arm studies by using a regulation for regenerative medicine in 2016. The efficacy of Temcell was evaluated in 381 consecutive patients treated with Temcell during the initial 3 years after its approval. Interestingly, its real-world efficacy was found to be equivalent to that observed in a prospective study of remestemcel-L with strict eligibility criteria. In this article, the potential of MSC therapy in the treatment of acute GVHD is discussed. A meticulous comparison of studies of remestemcel-L and Temcell, remestemcel-L/Temcell and ruxolitinib, and remestemcel-L/Temcell and thymoglobulin showed that the precise position of remestemcel-L/Temcell therapy in the treatment of acute GVHD remains to be determined.

Keywords: graft-versus-host disease (GVHD); mesenchymal stem cell (MSC); ruxolitinib; steroid; thymoglobulin.

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Conflict of interest statement

MM has received honoraria from Kyowa Kirin, Sumitomo Dainippon Pharma, FUJIFILM, Toyama Chemical, Novartis Pharma, MSD, JCR Pharmaceuticals, Astellas Pharma, Miyarisan Pharmaceutical, Asahi Kasei Pharma, GlaxoSmithKline, Celgene and Otsuka Pharmaceutical. TT has received grants from Kyowa Kirin, Chugai, Sanofi, Astellas, TEIJIN PHARMA, Fuji Pharma and NIPPON SHINYAKU; personal fees from Novartis, Merck, Kyowa Kirin, Takeda, Pfizer and Bristol-Myers Squibb; and non-financial support from Janssen and Novartis.

Figures

Figure 1
Figure 1
Number of patients with (blue) and without (orange) overall response (OR) in each study of MSC therapy for acute GVHD. Total numbers and percentages of patients with or without OR as the sum of all reported cases are provided.
See this image and copyright information in PMC

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