Oligotide, a Defibrotide Derivative, Protects Human Microvascular Endothelial Cells Against Fludarabine-Induced Activation, Damage and Allogenicity.

Fludarabine is a non-myeloablative 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 anti-leukemic 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.