Children and adults with refractory acute graft-versus-host disease respond to treatment with the mesenchymal stromal cell preparation "MSC-FFM"—outcome report of 92 patients

  • (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.

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Author:Halvard-Björn BönigORCiDGND, Zyrafete Kuçi, Selim Kuçi, Shahrzad Bakhtiar, Oliver Basu, Gesine Bug, Mike Dennis, Johann Greil, Aniko Barta, Krisztián KállayORCiD, Peter Lang, Giovanna Lucchini, Raj Pol, Ansgar SchulzORCiDGND, Karl-Walter Sykora, Irene Teichert- von Lüttichau, Grit Herter-Sprie, Mohammad Ashab Uddin, Phil Jenkin, Abdulrahman AlsultanORCiD, Jochen Büchner, Jerry Stein, Agnes Kelemen, Andrea Jarisch, Jan Sörensen, Emilia Salzmann-Manrique, Martin Hutter, Richard Schäfer, Erhard SeifriedORCiDGND, Shankara Paneesha, Igor Novitzky-Basso, Aharon Gefen, Neta Nevo, Gernot Beutel, Paul-Gerhardt SchlegelGND, Thomas KlingebielORCiDGND, Peter BaderORCiDGND
Pubmed Id:
Parent Title (English):Cells
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/12/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/02/12
Tag:cell therapy; graft-versus host; hospital exemption; mesenchymal stromal cell; refractory aGvHD; steroid-resistant aGvHD; transplantation
Issue:12, Art. 1577
Page Number:13
First Page:1
Last Page:13
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0