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
Creators: name: Bonig, Halvard
name: Kuçi, Zyrafete
name: Kuçi, Selim
name: Bakhtiar, Shahrzad
name: Basu, Oliver
name: Bug, Gesine
name: Dennis, Mike
name: Greil, Johann
name: Barta, Aniko
name: Kállay, Krisztián M.
name: Lang, Peter
name: Lucchini, Giovanna
name: Pol, Raj
name: Schulz, Ansgar
name: Sykora, Karl-Walter
name: Teichert Von Luettichau, Irene
name: Herter-Sprie, Grit
name: Ashab Uddin, Mohammad
name: Jenkin, Phil
name: Alsultan, Abdulrahman
name: Buechner, Jochen
name: Stein, Jerry
name: Kelemen, Agnes
name: Jarisch, Andrea
name: Soerensen, Jan
name: Salzmann-Manrique, Emilia
name: Hutter, Martin
name: Schäfer, Richard
name: Seifried, Erhard
name: Paneesha, Shankara
name: Novitzky-Basso, Igor
name: Gefen, Aharon
name: Nevo, Neta
name: Beutel, Gernot
name: Schlegel, Paul-Gerhardt
name: Klingebiel, Thomas
name: Bader, Peter
Publisher: name: Universität Ulm
Year: 2019
Subjects: subject: Mesenchymal stromal cell
subject: Hospital exemption
subject: Steroid-resistant aGvHD
subject: Refractory aGvHD
subject: DDC 610 / Medicine &amp; health
subject: Graft vs host disease
subject: Transplantation
subject: Mesenchymal stem cells
subject: Cell- and tissue-based therapy
subject: Transplantat-Wirt-Reaktion
subject: Mesenchymzelle
subject: Steroide

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.