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Richardson, Paul G.; Murakami, Carol; Jin, Zhezhen; Warren, Diane; Momtaz, Parisa; Hoppensteadt, Deborah; Elias, Anthony D.; Antin, Joseph H.; Soiffer, Robert; Spitzer, Thomas; Avigan, David; Bearman, Scott I.; Martin, Paul L.; Kurtzberg, Joanne; Vredenburgh, James; Chen, Allen R.; Arai, Sally; Vogelsang, Georgia; McDonald, George B.; Guinan, Eva C.
Blood, 12/2002, Letnik: 100, Številka: 13Journal Article
Veno-occlusive disease (VOD) is the most common regimen-related toxicity accompanying stem cell transplantation (SCT). Severe VOD complicated by multisystem organ failure (MOF) remains almost uniformly fatal. Preliminary experience with defibrotide (DF), a single-stranded polydeoxyribonucleotide with fibrinolytic, antithrombotic, 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 76.95 μM (4.5 mg/dL), median weight gain was 7%, ascites was present in 84%, and abnormal hepatic portal venous flow was present in 35%. At DF initiation, median bilirubin had increased to 215.46 μM (12.6 mg/dL), and MOF was present in 97%. DF was administered intravenously in doses ranging from 5 to 60 mg/kg per 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, whereas busulfan-based conditioning and encephalopathy predicted worse outcome. Decreases in mean creatinine and plasminogen activator inhibitor 1(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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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