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

Cells. 2019 Dec 5;8(12):1577. doi: 10.3390/cells8121577.

Abstract

(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.

Keywords: cell therapy; graft-versus host; hospital exemption; mesenchymal stromal cell; refractory aGvHD; steroid-resistant aGvHD; transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bone Marrow Transplantation / adverse effects
  • Cell- and Tissue-Based Therapy* / adverse effects
  • Cell- and Tissue-Based Therapy* / methods
  • Child
  • Child, Preschool
  • Female
  • Graft vs Host Disease / diagnosis
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Disease / therapy*
  • Humans
  • Infant
  • Male
  • Mesenchymal Stem Cell Transplantation* / adverse effects
  • Mesenchymal Stem Cell Transplantation* / methods
  • Mesenchymal Stem Cells*
  • Middle Aged
  • Transplantation Conditioning
  • Treatment Outcome
  • Young Adult