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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 t...

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Autores principales: Bonig, Halvard, Kuçi, Zyrafete, Kuçi, Selim, Bakhtiar, Shahrzad, Basu, Oliver, Bug, Gesine, Dennis, Mike, Greil, Johann, Barta, Aniko, Kállay, Krisztián M., Lang, Peter, Lucchini, Giovanna, Pol, Raj, Schulz, Ansgar, Sykora, Karl-Walter, Teichert von Luettichau, Irene, Herter-Sprie, Grit, Ashab Uddin, Mohammad, Jenkin, Phil, Alsultan, Abdulrahman, Buechner, Jochen, Stein, Jerry, Kelemen, Agnes, Jarisch, Andrea, Soerensen, Jan, Salzmann-Manrique, Emilia, Hutter, Martin, Schäfer, Richard, Seifried, Erhard, Paneesha, Shankara, Novitzky-Basso, Igor, Gefen, Aharon, Nevo, Neta, Beutel, Gernot, Schlegel, Paul-Gerhardt, Klingebiel, Thomas, Bader, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952775/
https://www.ncbi.nlm.nih.gov/pubmed/31817480
http://dx.doi.org/10.3390/cells8121577
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author Bonig, Halvard
Kuçi, Zyrafete
Kuçi, Selim
Bakhtiar, Shahrzad
Basu, Oliver
Bug, Gesine
Dennis, Mike
Greil, Johann
Barta, Aniko
Kállay, Krisztián M.
Lang, Peter
Lucchini, Giovanna
Pol, Raj
Schulz, Ansgar
Sykora, Karl-Walter
Teichert von Luettichau, Irene
Herter-Sprie, Grit
Ashab Uddin, Mohammad
Jenkin, Phil
Alsultan, Abdulrahman
Buechner, Jochen
Stein, Jerry
Kelemen, Agnes
Jarisch, Andrea
Soerensen, Jan
Salzmann-Manrique, Emilia
Hutter, Martin
Schäfer, Richard
Seifried, Erhard
Paneesha, Shankara
Novitzky-Basso, Igor
Gefen, Aharon
Nevo, Neta
Beutel, Gernot
Schlegel, Paul-Gerhardt
Klingebiel, Thomas
Bader, Peter
author_facet Bonig, Halvard
Kuçi, Zyrafete
Kuçi, Selim
Bakhtiar, Shahrzad
Basu, Oliver
Bug, Gesine
Dennis, Mike
Greil, Johann
Barta, Aniko
Kállay, Krisztián M.
Lang, Peter
Lucchini, Giovanna
Pol, Raj
Schulz, Ansgar
Sykora, Karl-Walter
Teichert von Luettichau, Irene
Herter-Sprie, Grit
Ashab Uddin, Mohammad
Jenkin, Phil
Alsultan, Abdulrahman
Buechner, Jochen
Stein, Jerry
Kelemen, Agnes
Jarisch, Andrea
Soerensen, Jan
Salzmann-Manrique, Emilia
Hutter, Martin
Schäfer, Richard
Seifried, Erhard
Paneesha, Shankara
Novitzky-Basso, Igor
Gefen, Aharon
Nevo, Neta
Beutel, Gernot
Schlegel, Paul-Gerhardt
Klingebiel, Thomas
Bader, Peter
author_sort Bonig, Halvard
collection PubMed
description (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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spelling pubmed-69527752020-01-23 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 Bonig, Halvard Kuçi, Zyrafete Kuçi, Selim Bakhtiar, Shahrzad Basu, Oliver Bug, Gesine Dennis, Mike Greil, Johann Barta, Aniko Kállay, Krisztián M. Lang, Peter Lucchini, Giovanna Pol, Raj Schulz, Ansgar Sykora, Karl-Walter Teichert von Luettichau, Irene Herter-Sprie, Grit Ashab Uddin, Mohammad Jenkin, Phil Alsultan, Abdulrahman Buechner, Jochen Stein, Jerry Kelemen, Agnes Jarisch, Andrea Soerensen, Jan Salzmann-Manrique, Emilia Hutter, Martin Schäfer, Richard Seifried, Erhard Paneesha, Shankara Novitzky-Basso, Igor Gefen, Aharon Nevo, Neta Beutel, Gernot Schlegel, Paul-Gerhardt Klingebiel, Thomas Bader, Peter Cells Article (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. MDPI 2019-12-05 /pmc/articles/PMC6952775/ /pubmed/31817480 http://dx.doi.org/10.3390/cells8121577 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bonig, Halvard
Kuçi, Zyrafete
Kuçi, Selim
Bakhtiar, Shahrzad
Basu, Oliver
Bug, Gesine
Dennis, Mike
Greil, Johann
Barta, Aniko
Kállay, Krisztián M.
Lang, Peter
Lucchini, Giovanna
Pol, Raj
Schulz, Ansgar
Sykora, Karl-Walter
Teichert von Luettichau, Irene
Herter-Sprie, Grit
Ashab Uddin, Mohammad
Jenkin, Phil
Alsultan, Abdulrahman
Buechner, Jochen
Stein, Jerry
Kelemen, Agnes
Jarisch, Andrea
Soerensen, Jan
Salzmann-Manrique, Emilia
Hutter, Martin
Schäfer, Richard
Seifried, Erhard
Paneesha, Shankara
Novitzky-Basso, Igor
Gefen, Aharon
Nevo, Neta
Beutel, Gernot
Schlegel, Paul-Gerhardt
Klingebiel, Thomas
Bader, Peter
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952775/
https://www.ncbi.nlm.nih.gov/pubmed/31817480
http://dx.doi.org/10.3390/cells8121577
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