TY - JOUR
T1 - Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure
T2 - Response without significant toxicity in a high-risk population and factors predictive of outcome
AU - Richardson, Paul G.
AU - Murakami, Carol
AU - Jin, Zhezhen
AU - Warren, Diane
AU - Momtaz, Parisa
AU - Hoppensteadt, Deborah
AU - Elias, Anthony D.
AU - Antin, Joseph H.
AU - Soiffer, Robert
AU - Spitzer, Thomas
AU - Avigan, David
AU - Bearman, Scott I.
AU - Martin, Paul L.
AU - Kurtzberg, Joanne
AU - Vredenburgh, James
AU - Chen, Allen R.
AU - Arai, Sally
AU - Vogelsang, Georgia
AU - McDonald, George B.
AU - Guinan, Eva C.
PY - 2002/12/15
Y1 - 2002/12/15
N2 - 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(PAl-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.
AB - 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(PAl-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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U2 - 10.1182/blood-2002-04-1216
DO - 10.1182/blood-2002-04-1216
M3 - Article
C2 - 12393437
AN - SCOPUS:0037114746
SN - 0006-4971
VL - 100
SP - 4337
EP - 4343
JO - Blood
JF - Blood
IS - 13
ER -