1. ¹Department of Hematology and Oncology, University of Regensburg, Germany
2. ²Gentium, Sp.A., Como, Italy

Correspondence: Dr G Eissner, Department of Hematology and Oncology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. E-mail: guenther.eissner@klinik.uni-regensburg.de

Received 13 September 2004; Accepted 10 January 2005; Published online 21 March 2005.

Abstract

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.