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The use of MSCs in steroid-refractory acute GvHD in Europe: a survey from the EBMT cellular therapy & immunobiology working party

Bone Marrow Transplantation volume 60, pages 708–714 (2025)Cite this article

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Abstract

Acute graft-versus-host disease (aGvHD) remains a significant complication of allogeneic hematopoietic cell transplantation, with 40% of patients failing to respond to high-dose steroids. Ruxolitinib has become the standard treatment for steroid-refractory aGvHD (SR-GvHD), but its failure in approximately one-third of cases highlights the need for alternative therapies. Mesenchymal stromal cells (MSCs), known for their immunomodulatory properties, are suggested as a treatment option, but their role in SR-GvHD remains unclear. To better understand MSC therapy outcomes, the EBMT Cellular Therapy & Immunobiology Working Party conducted a survey of centers treating >20 SR-GvHD patients with MSCs between 2007 and 2020. Data from 313 patients were analyzed, revealing a 44.5% overall response rate at day 28. Responders at day 7 had a higher likelihood of maintaining responses by day 28. Using a landmark analysis, the overall survival at 12 months, conditional on being alive at day 28, was 39.2%. Survival at 12 months was 48.6% for responders, compared to 24.4% for non-responders. Despite manufacturing variabilities, MSCs produced by academic pharma appear effective in SR-GvHD, offering a viable treatment alternative for heavily pretreated patients. These findings support further investigation of MSCs to establish standardized protocols and validate their efficacy as third-line therapy for SR-GvHD.

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Fig. 1: GvHD grade per timepoint, and proportion of response on day 7 and day 28.
Fig. 2: Overall survival.
Fig. 3: Relapse, non-relapse mortality and relapse-free survival.

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Author information

Authors and Affiliations

  1. Department of Hematology, University Medical Centre Utrecht, Utrecht, The Netherlands

    L. G. M. Daenen, L. E. van der Wagen & J. Kuball

  2. EBMT Study Unit, Leiden, The Netherlands

    E. F. Bonneville & J. D. Hoogenboom

  3. Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands

    E. F. Bonneville & L. C. de Wreede

  4. Hematology Department. Hospital Universitario de Salamanca (Spain), IBSAL, CIBERONC. Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain

    L. López-Corral

  5. Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania

    A. Bukauskas

  6. University Hospital Dresden, TU Dresden, Dresden, Germany

    M. Bornhäuser

  7. CHU of Liege and University of Liege, Liege, Belgium

    Y. Beguin

  8. Turku University Hospital, Turku, Finland

    M. Itäla-Remes

  9. Service d’Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), INSERM, Paris, France

    F. Malard

  10. Institut Paoli-Calmettes, Centre de Lutte Contre le Cancer; Centre d’Investigations Cliniques en Biothérapies, Université d’Aix-Marseille, Inserm, CBT 1409, Marseille, France

    C. Chabannon

  11. Comprehensive Cancer Centre, King’s College London, London, UK

    F. Dazzi

  12. San Raffaele Scientific Institute, Hematology and Bone marrow Transplantation Unit, Milan, Italy

    A. Ruggeri

Authors
  1. L. G. M. Daenen
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  2. L. E. van der Wagen
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  3. E. F. Bonneville
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  4. L. López-Corral
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  5. A. Bukauskas
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  6. M. Bornhäuser
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  7. Y. Beguin
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  8. M. Itäla-Remes
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  9. J. D. Hoogenboom
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  10. L. C. de Wreede
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  11. F. Malard
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  12. C. Chabannon
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  13. F. Dazzi
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  14. A. Ruggeri
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  15. J. Kuball
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Contributions

LGMD and JK performed analyses, created tables and wrote the manuscript. LEvdW, LLC, AB, MB, YB and MIR were responsible physicians at the hospitals where the patients were treated. They provided the data for the report. FD created the questionnaires. JDH performed data management. EFB performed data analysis, statistical analyses and created the figures. LCdW supervised the statical analyses. FM, CC, FD and AR provided feedback on the report.

Corresponding author

Correspondence to J. Kuball.

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The authors declare no competing interests.

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Daenen, L.G.M., van der Wagen, L.E., Bonneville, E.F. et al. The use of MSCs in steroid-refractory acute GvHD in Europe: a survey from the EBMT cellular therapy & immunobiology working party. Bone Marrow Transplant 60, 708–714 (2025). https://doi.org/10.1038/s41409-025-02531-3

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