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Post-Transplant Events

Oligotide, a defibrotide derivative, protects human microvascular endothelial cells against fludarabine-induced activation, damage and allogenicity

Bone Marrow Transplantation volume 35, pages 915–920 (2005)Cite this article

Summary:

Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a component of alternative reduced-intensity conditioning regimens prior to allogeneic stem cell transplantation (SCT). However, we have previously shown that 2-fluoroadenine 9-beta- D-arabinofuranoside (F-Ara) as the active metabolized form of fludarabine induces damage, activation and allogenicity in human microvascular endothelial cells (HMEC). We had also identified the pharmaceutic compound Defibrotide (DF), originally used in the treatment of veno-occlusive disease and thrombotic microangiopathy, as being protective against F-Ara-induced dysfunction of HMEC, importantly, without affecting the antileukemic effect of F-Ara. In the present report, we show that a recently developed derivative of DF, Oligotide, similarly downregulates F-Ara-induced activation and damage of HMEC as well as their antigenicity for allogeneic CD8+ T cells. In addition, Oligotide could also block F-Ara-mediated transendothelial migration of peripheral blood cells across the HMEC barrier. Taken together, these observations argue for a potential clinical use of both DF and Oligotide in pre transplant conditioning.

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Acknowledgements

This work is supported by grant No. Ei68/2-3 from the Deutsche Forschungsgemeinschaft (DFG) and the Marie Curie Research Training Network of the 6th Framework Programme of the European Commission.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University of Regensburg, Germany

    G Eissner, S Blüml, V Burger, S Haffner, R Andreesen & E Holler

  2. Gentium, Sp.A., Como, Italy

    G Eissner & M Iacobelli

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  1. G Eissner
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  2. M Iacobelli
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  4. V Burger
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  7. E Holler
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Correspondence to G Eissner.

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Eissner, G., Iacobelli, M., Blüml, S. et al. Oligotide, a defibrotide derivative, protects human microvascular endothelial cells against fludarabine-induced activation, damage and allogenicity. Bone Marrow Transplant 35, 915–920 (2005). https://doi.org/10.1038/sj.bmt.1704930

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