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.
Highlights
Much progress has been made in allogeneic transplantation
FFM, with a 76% overall response probability including 43% complete responses at last follow-up patients were significantly unfavorable, with a hazard ratio of 0.35
SR-aGvHD patients were significantly unfavorable, with a hazard ratio of 0.35
Summary
Much progress has been made in allogeneic transplantation. Improvements include more refined HLA typing, larger donor registries providing better-matched donors, better insight into graft-versus-host disease (GvHD)-associated donor properties and better options for GvHD prophylaxis.Yet the number of patients developing severe refractory acute GvHD (R-aGvHD) has not decreased.Approximately one in nine transplant recipients will develop this complication. Much progress has been made in allogeneic transplantation. Improvements include more refined HLA typing, larger donor registries providing better-matched donors, better insight into graft-versus-host disease (GvHD)-associated donor properties and better options for GvHD prophylaxis. The number of patients developing severe refractory acute GvHD (R-aGvHD) has not decreased. One in nine transplant recipients will develop this complication. Approximately patients/year in Europe and 4000 patients/year world-wide, will be affected. For these patients, prognosis remains guarded as a wide panel of immunosuppressive medicines have been explored and failed [1]. The most recent large study estimates the 6-month and 4-year survival of R-aGvHD at 40%
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
