Treatment of chronic GvHD with mesenchymal stromal cells induces durable responses: A phase II study.

Autor: Boberg E; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden., von Bahr L; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Afram G; Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.; Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden., Lindström C; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden., Ljungman P; Department of Medicine, Karolinska Institutet Huddinge, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden., Heldring N; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Petzelbauer P; Skin and Endothelial Research Division, Department of Dermatology, Medical University of Vienna, Vienna, Austria., Garming Legert K; Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden., Kadri N; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden., Le Blanc K; Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Stem cells translational medicine [Stem Cells Transl Med] 2020 Oct; Vol. 9 (10), pp. 1190-1202. Date of Electronic Publication: 2020 Jun 23.
DOI: 10.1002/sctm.20-0099
Abstrakt: Steroid-refractory chronic graft-vs-host disease (cGvHD) contributes to morbidity after allogeneic hematopoietic stem cell transplantation. Here, we report on 11 patients with severe, refractory cGvHD treated with repeated infusions of allogeneic bone marrow-derived mesenchymal stromal cells (MSC) over a 6- to 12-month period. Six patients responded to MSC treatment following National Institutes of Health response criteria, accompanied by improvement in GvHD-related symptoms and quality of life. This response was durable, with systemic immunosuppressive therapy withdrawn from two responders, and a further two free from steroids and tapering calcineurin inhibitors. All responders displayed a distinct immune phenotype characterized by higher levels of naïve T cells and B cells before treatment compared with the nonresponders, and a significantly higher fraction of CD31+ naïve CD4+ T cells. MSC treatment was associated with significant increases in naïve T cells, B cells, and Tregs 7 days after each infusion. Skin biopsies showed resolution of epidermal pathology. CXCL9 and CXCL10 showed differential responses in responder and nonresponder patients. Our data support the use of MSC infusions as treatment for steroid-refractory cGvHD with durable responses. We propose CXCL9 and CXCL10 as early biomarkers for responsiveness to MSC treatment. Our results highlight the importance of the MSC recipient immune phenotype in promoting treatment response. This trial was registered at www.ClinicalTrials.gov as #NCT01522716.
(© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)
Databáze: MEDLINE
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