Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: Response without significant toxicity in a high-risk population and factors predictive of outcome

Paul G. Richardson, Carol Murakami, Zhezhen Jin, Diane Warren, Parisa Momtaz, Deborah Hoppensteadt, Anthony D. Elias, Joseph H. Antin, Robert Soiffer, Thomas Spitzer, David Avigan, Scott I. Bearman, Paul L. Martin, Joanne Kurtzberg, James Vredenburgh, Allen R. Chen, Sally Arai, Georgia Vogelsang, George B. McDonald, Eva C. Guinan

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4337-4343
Number of pages7
JournalBlood
Volume100
Issue number13
DOIs
StatePublished - Dec 15 2002

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Stem Cell Transplantation
Stem cells
Toxicity
Population
Bilirubin
Survival
Polydeoxyribonucleotides
Therapeutics
defibrotide
Busulfan
Plasminogen Activator Inhibitor 1
Brain Diseases
Ascites
Weight Gain
Creatinine
Survival Rate
Hemorrhage
Safety
Liver

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure : Response without significant toxicity in a high-risk population and factors predictive of outcome. / 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.

In: Blood, Vol. 100, No. 13, 15.12.2002, p. 4337-4343.

Research output: Contribution to journalArticle

Richardson, PG, Murakami, C, Jin, Z, Warren, D, Momtaz, P, Hoppensteadt, D, Elias, AD, Antin, JH, Soiffer, R, Spitzer, T, Avigan, D, Bearman, SI, Martin, PL, Kurtzberg, J, Vredenburgh, J, Chen, AR, Arai, S, Vogelsang, G, McDonald, GB & Guinan, EC 2002, 'Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: Response without significant toxicity in a high-risk population and factors predictive of outcome', Blood, vol. 100, no. 13, pp. 4337-4343. https://doi.org/10.1182/blood-2002-04-1216
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. / Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure : Response without significant toxicity in a high-risk population and factors predictive of outcome. In: Blood. 2002 ; Vol. 100, No. 13. pp. 4337-4343.
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abstract = "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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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

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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.

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