Treatment of severe veno-occlusive disease with defibrotide : Compassionate use results in response without significant toxicity in a high-risk population
Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) i...
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| Veröffentlicht in: | Blood 1998-08, Vol.92 (3), p.737-744 |
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| creator | RICHARDSON, P. G ELIAS, A. D SOIFFER, R VREDENBURGH, J LILL, M WOOLFREY, A. E BEARMAN, S. I LACOBELLI, M FAREED, J GUINAN, E. C KRISHNAN, A WHEELER, C NATH, R HOPPENSTEADT, D KINCHLA, N. M NEUBERG, D WALLER, E. K ANTIN, J. H |
| description | Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin |
| format | Article |
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G ; ELIAS, A. D ; SOIFFER, R ; VREDENBURGH, J ; LILL, M ; WOOLFREY, A. E ; BEARMAN, S. I ; LACOBELLI, M ; FAREED, J ; GUINAN, E. C ; KRISHNAN, A ; WHEELER, C ; NATH, R ; HOPPENSTEADT, D ; KINCHLA, N. M ; NEUBERG, D ; WALLER, E. K ; ANTIN, J. H</creator><creatorcontrib>RICHARDSON, P. G ; ELIAS, A. D ; SOIFFER, R ; VREDENBURGH, J ; LILL, M ; WOOLFREY, A. E ; BEARMAN, S. I ; LACOBELLI, M ; FAREED, J ; GUINAN, E. C ; KRISHNAN, A ; WHEELER, C ; NATH, R ; HOPPENSTEADT, D ; KINCHLA, N. M ; NEUBERG, D ; WALLER, E. K ; ANTIN, J. H</creatorcontrib><description>Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>PMID: 9680339</identifier><language>eng</language><publisher>Washington, DC: The Americain Society of Hematology</publisher><subject>Adolescent ; Adult ; Bilirubin - blood ; Biological and medical sciences ; Cardiovascular system ; Child ; Child, Preschool ; Drug Evaluation ; Feasibility Studies ; Female ; Fibrinolytic Agents - adverse effects ; Fibrinolytic Agents - therapeutic use ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hemorrhage - chemically induced ; Heparin - therapeutic use ; Hepatic Veno-Occlusive Disease - drug therapy ; Hepatic Veno-Occlusive Disease - mortality ; Humans ; Male ; Medical sciences ; Miscellaneous ; Multiple Organ Failure - prevention & control ; Neoplasms - mortality ; Neoplasms - therapy ; Palliative Care ; Pharmacology. Drug treatments ; Polydeoxyribonucleotides - adverse effects ; Polydeoxyribonucleotides - therapeutic use ; Receptors, Purinergic P1 - drug effects ; Retrospective Studies ; Risk ; Thalassemia - therapy ; Tissue Plasminogen Activator - therapeutic use ; Treatment Outcome</subject><ispartof>Blood, 1998-08, Vol.92 (3), p.737-744</ispartof><rights>1998 INIST-CNRS</rights><rights>Copyright 1998 by The American Society of Hematology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2358119$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9680339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>RICHARDSON, P. G</creatorcontrib><creatorcontrib>ELIAS, A. D</creatorcontrib><creatorcontrib>SOIFFER, R</creatorcontrib><creatorcontrib>VREDENBURGH, J</creatorcontrib><creatorcontrib>LILL, M</creatorcontrib><creatorcontrib>WOOLFREY, A. E</creatorcontrib><creatorcontrib>BEARMAN, S. I</creatorcontrib><creatorcontrib>LACOBELLI, M</creatorcontrib><creatorcontrib>FAREED, J</creatorcontrib><creatorcontrib>GUINAN, E. C</creatorcontrib><creatorcontrib>KRISHNAN, A</creatorcontrib><creatorcontrib>WHEELER, C</creatorcontrib><creatorcontrib>NATH, R</creatorcontrib><creatorcontrib>HOPPENSTEADT, D</creatorcontrib><creatorcontrib>KINCHLA, N. M</creatorcontrib><creatorcontrib>NEUBERG, D</creatorcontrib><creatorcontrib>WALLER, E. K</creatorcontrib><creatorcontrib>ANTIN, J. H</creatorcontrib><title>Treatment of severe veno-occlusive disease with defibrotide : Compassionate use results in response without significant toxicity in a high-risk population</title><title>Blood</title><addtitle>Blood</addtitle><description>Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Bilirubin - blood</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Drug Evaluation</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Fibrinolytic Agents - adverse effects</subject><subject>Fibrinolytic Agents - therapeutic use</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Hemorrhage - chemically induced</subject><subject>Heparin - therapeutic use</subject><subject>Hepatic Veno-Occlusive Disease - drug therapy</subject><subject>Hepatic Veno-Occlusive Disease - mortality</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Multiple Organ Failure - prevention & control</subject><subject>Neoplasms - mortality</subject><subject>Neoplasms - therapy</subject><subject>Palliative Care</subject><subject>Pharmacology. Drug treatments</subject><subject>Polydeoxyribonucleotides - adverse effects</subject><subject>Polydeoxyribonucleotides - therapeutic use</subject><subject>Receptors, Purinergic P1 - drug effects</subject><subject>Retrospective Studies</subject><subject>Risk</subject><subject>Thalassemia - therapy</subject><subject>Tissue Plasminogen Activator - therapeutic use</subject><subject>Treatment Outcome</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kN1Kw0AQhRdRaq0-grAX3gZms_mrd1L8g4I39bpMNrPtaJIN2U21r-LTmmLwag6cb84c5kzMVRoXEUAM52IOAFmULHN1Ka68_wBQiY7TmZgtswK0Xs7Fz6YnDA21QTorPR2oJ3mg1kXOmHrwfCBZsSf0JL847GVFlsveBa5I3suVazr0nl2LgeQwQj35oQ5ecnuSnWunRTcE6XnXsmWD47XgvtlwOJ5AlHve7aOe_afsXDfUGMbEa3FhsfZ0M82FeH963KxeovXb8-vqYR11sU5DhKrKLFGRFSouMEXIYgRtMSkJSqvQmJwMQa6BdFplOrcVFgBJpnROubF6IW7_cruhbKjadj032B-3049G_27y0RusbY-tYf-PjSUKpZb6Fx7MdbM</recordid><startdate>19980801</startdate><enddate>19980801</enddate><creator>RICHARDSON, P. G</creator><creator>ELIAS, A. D</creator><creator>SOIFFER, R</creator><creator>VREDENBURGH, J</creator><creator>LILL, M</creator><creator>WOOLFREY, A. E</creator><creator>BEARMAN, S. I</creator><creator>LACOBELLI, M</creator><creator>FAREED, J</creator><creator>GUINAN, E. C</creator><creator>KRISHNAN, A</creator><creator>WHEELER, C</creator><creator>NATH, R</creator><creator>HOPPENSTEADT, D</creator><creator>KINCHLA, N. M</creator><creator>NEUBERG, D</creator><creator>WALLER, E. K</creator><creator>ANTIN, J. H</creator><general>The Americain Society of Hematology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>19980801</creationdate><title>Treatment of severe veno-occlusive disease with defibrotide : Compassionate use results in response without significant toxicity in a high-risk population</title><author>RICHARDSON, P. G ; ELIAS, A. D ; SOIFFER, R ; VREDENBURGH, J ; LILL, M ; WOOLFREY, A. E ; BEARMAN, S. I ; LACOBELLI, M ; FAREED, J ; GUINAN, E. C ; KRISHNAN, A ; WHEELER, C ; NATH, R ; HOPPENSTEADT, D ; KINCHLA, N. M ; NEUBERG, D ; WALLER, E. K ; ANTIN, J. 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Drug treatments</topic><topic>Polydeoxyribonucleotides - adverse effects</topic><topic>Polydeoxyribonucleotides - therapeutic use</topic><topic>Receptors, Purinergic P1 - drug effects</topic><topic>Retrospective Studies</topic><topic>Risk</topic><topic>Thalassemia - therapy</topic><topic>Tissue Plasminogen Activator - therapeutic use</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>RICHARDSON, P. G</creatorcontrib><creatorcontrib>ELIAS, A. D</creatorcontrib><creatorcontrib>SOIFFER, R</creatorcontrib><creatorcontrib>VREDENBURGH, J</creatorcontrib><creatorcontrib>LILL, M</creatorcontrib><creatorcontrib>WOOLFREY, A. E</creatorcontrib><creatorcontrib>BEARMAN, S. I</creatorcontrib><creatorcontrib>LACOBELLI, M</creatorcontrib><creatorcontrib>FAREED, J</creatorcontrib><creatorcontrib>GUINAN, E. C</creatorcontrib><creatorcontrib>KRISHNAN, A</creatorcontrib><creatorcontrib>WHEELER, C</creatorcontrib><creatorcontrib>NATH, R</creatorcontrib><creatorcontrib>HOPPENSTEADT, D</creatorcontrib><creatorcontrib>KINCHLA, N. M</creatorcontrib><creatorcontrib>NEUBERG, D</creatorcontrib><creatorcontrib>WALLER, E. K</creatorcontrib><creatorcontrib>ANTIN, J. H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>RICHARDSON, P. G</au><au>ELIAS, A. D</au><au>SOIFFER, R</au><au>VREDENBURGH, J</au><au>LILL, M</au><au>WOOLFREY, A. E</au><au>BEARMAN, S. I</au><au>LACOBELLI, M</au><au>FAREED, J</au><au>GUINAN, E. C</au><au>KRISHNAN, A</au><au>WHEELER, C</au><au>NATH, R</au><au>HOPPENSTEADT, D</au><au>KINCHLA, N. M</au><au>NEUBERG, D</au><au>WALLER, E. K</au><au>ANTIN, J. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of severe veno-occlusive disease with defibrotide : Compassionate use results in response without significant toxicity in a high-risk population</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1998-08-01</date><risdate>1998</risdate><volume>92</volume><issue>3</issue><spage>737</spage><epage>744</epage><pages>737-744</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation.</abstract><cop>Washington, DC</cop><pub>The Americain Society of Hematology</pub><pmid>9680339</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Blood, 1998-08, Vol.92 (3), p.737-744 |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adolescent Adult Bilirubin - blood Biological and medical sciences Cardiovascular system Child Child, Preschool Drug Evaluation Feasibility Studies Female Fibrinolytic Agents - adverse effects Fibrinolytic Agents - therapeutic use Hematopoietic Stem Cell Transplantation - adverse effects Hemorrhage - chemically induced Heparin - therapeutic use Hepatic Veno-Occlusive Disease - drug therapy Hepatic Veno-Occlusive Disease - mortality Humans Male Medical sciences Miscellaneous Multiple Organ Failure - prevention & control Neoplasms - mortality Neoplasms - therapy Palliative Care Pharmacology. Drug treatments Polydeoxyribonucleotides - adverse effects Polydeoxyribonucleotides - therapeutic use Receptors, Purinergic P1 - drug effects Retrospective Studies Risk Thalassemia - therapy Tissue Plasminogen Activator - therapeutic use Treatment Outcome |
| title | Treatment of severe veno-occlusive disease with defibrotide : Compassionate use results in response without significant toxicity in a high-risk population |
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