Defibrotide inhibits donor leucocyte-endothelial interactions and protects against acute graft-versus-host disease.

Journal of Cellular and Molecular Medicine
David García-BernalJose M Moraleda

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective therapy for the treatment of high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. Acute graft-versus-host disease (aGvHD) remains the most frequent cause of non-relapse mortality following allo-HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi-target drug successfully employed for prophylaxis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo-HCT. Using a fully MHC-mismatched murine model of allo-HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD-associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo-HCT. Moreover, we performed in vitro mechanistic...Continue Reading

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Citations

Feb 5, 2021·British Journal of Haematology·Eleonora CalabrettaPaul Richardson
Jun 8, 2021·Cardiovascular Drugs and Therapy·Pedro CastroMaribel Diaz-Ricart
Jun 26, 2021·Expert Opinion on Therapeutic Targets·Edward RichardsonJose M Moraleda
Aug 24, 2021·Frontiers in Immunology·Melrine PereiraMaithili Sashindranath
Sep 18, 2021·Current Opinion in Hematology·Michelle SchoettlerLeslie Lehmann

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Methods Mentioned

BETA
density gradient centrifugation
flow cytometry

Software Mentioned

ImageJ

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