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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2002-04-1216. This Article Full Text (PDF) All Versions of this Article: 2002-04-1216v1 100/13/4337    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Richardson, P. G Articles by Guinan, E. C Search for Related Content PubMed PubMed Citation Articles by Richardson, P. G Articles by Guinan, E. C Social Bookmarking                   What's this? Submitted April 24, 2002 Accepted July 17, 2002 Multi-institutional use of defibrotide in 88 patients post stem cell transplant with severe veno-occlusive disease and multi-system organ failure; response without significant toxicity in a high risk population and factors predictive of outcome Paul G Richardson*, Carol Murakami, Zhezhen Jin, Diane L Warren, Parisa Momtaz, Deborah Hoppensteadt, Anthony D Elias, Joseph H Antin, Robert J Soiffer, Thomas R Spitzer, David Avigan, Scott I Bearman, Paul L Martin, Joanne Kurtzberg, James Vredenburgh, Allen R Chen, Sally Arai, Georgia Vogelsang, George B McDonald, and Eva C Guinan * Corresponding author; email: paul_richardson{at}dfci.harvard.edu. Veno-occlusive disease (VOD) is the most common regimen-related toxicity accompanying stem cell transplant (SCT). Severe VOD complicated by multi-system organ failure (MOF) remains almost uniformly fatal. Preliminary experience with Defibrotide (DF), a single stranded polydeoxyribonucleotide with fibrinolytic, anti-thrombotic and anti-ischemic properties, in the treatment for severe VOD has suggested safety and activity. Eighty-eight patients who developed severe VOD after SCT were treated with DF under a defined treatment plan. At diagnosis, median bilirubin was 4.5 mg/dL; median weight gain was 7%, ascites was present in 84% and abnormal hepatic portal venous flow in 35%. At DF initiation, median bilirubin had increased to 12.6 mg/dL and MOF was present in 97%. DF was administered intravenously in doses ranging from 5-60 mg/kg/day for a median of 15 days. No severe hemorrhage or other serious toxicity related to DF was reported. Complete resolution of VOD was seen in 36%, with 35% survival at day + 100. Predictors of survival included younger age, autologous SCT and abnormal portal flow, while busulfan-based conditioning and encephalopathy predicted worse outcome. Decreases in mean creatinine and PAI-1 levels during DF therapy predicted better survival. The complete response rate, survival to day + 100, and absence of significant DF-associated toxicity in this largest patient cohort reported to date confirm the results of earlier studies. Certain features associated with successful outcome may correlate with DF-related treatment effects, and prospective evaluation of DF therapy for severe VOD should allow better definition of predictors of response or failure. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C.A. Stein, S. Wu, A. M. Voskresenskiy, J.-F. Zhou, J. Shin, P. Miller, N. Souleimanian, and L. Benimetskaya G3139, an Anti-Bcl-2 Antisense Oligomer That Binds Heparin-Binding Growth Factors and Collagen I, Alters In vitro Endothelial Cell Growth and Tubular Morphogenesis Clin. Cancer Res., April 15, 2009; 15(8): 2797 - 2807. [Abstract] [Full Text] [PDF] C. 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