Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).

2.50
Hdl Handle:
http://hdl.handle.net/10541/78937
Title:
Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).
Authors:
Kaleelrahman, M; Eaton, J D; Leeming, David; Bowyer, K; Taberner, D; Chang, J; Scarffe, J Howard; Chopra, Rajesh
Abstract:
Hepatic veno-occlusive disease (VOD) is a common and potentially fatal complication of high dose chemotherapy with allogeneic/autologous stem cell transplant (SCT). The diagnosis and treatment of hepatic VOD is controversial. Clinical features are non-specific and may be mimicked by a number of other conditions causing hyperbilirubinaemia post-transplantation. Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a specific marker of VOD [1]. Defibrotide (DF) is a polydeoxyribonucleotide, which has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anti-coagulation. Recent evidence [2,3] suggests that use of DF in patients with severe VOD results in a promising response rate without attributable significant toxicity. Between January 1998 and July 1999, PAI-1 levels were measured serially in 16 patients undergoing SCT who had subsequently developed hyperbilirubinaemia. Diagnosis of VOD was made by established clinical criteria [4,5]. At the time of diagnosis, PAI-1 levels (mean+/-SD) were significantly elevated in patients with VOD (90.7+/-47 ng/ml, n=7) when compared with patients with jaundice from other causes post transplantation (12.1+/-6.4 ng/ml, n=9). Five of the patients with VOD received treatment with DF. Four out of five patients showed an initial response to DF (significant fall in bilirubin and improvement in other signs/symptoms) with one of these patients having a complete response (bilirubin < 2.0 mg/dl and full resolution of signs/symptoms and end-organ toxicity). Following treatment with DF, a corresponding fall in PAI-1 levels was noted in those responding, with non-responders maintaining raised levels. Conclusion: Raised PAI-1 levels post stem cell transplant are specific for VOD and a subsequent decrease in levels following treatment with DF may be associated with response to treatment.
Affiliation:
Departments of Medical Oncology and Haematology, Christie Hospital, Wilmslow Rd, Manchester, UK.
Citation:
Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF). 2003, 8 (2):91-5 Hematology
Journal:
Hematology
Issue Date:
Apr-2003
URI:
http://hdl.handle.net/10541/78937
DOI:
10.1080/1024533031000084231
PubMed ID:
12745658
Type:
Article
Language:
en
ISSN:
1024-5332
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorKaleelrahman, M-
dc.contributor.authorEaton, J D-
dc.contributor.authorLeeming, David-
dc.contributor.authorBowyer, K-
dc.contributor.authorTaberner, D-
dc.contributor.authorChang, J-
dc.contributor.authorScarffe, J Howard-
dc.contributor.authorChopra, Rajesh-
dc.date.accessioned2009-08-27T14:49:44Z-
dc.date.available2009-08-27T14:49:44Z-
dc.date.issued2003-04-
dc.identifier.citationRole of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF). 2003, 8 (2):91-5 Hematologyen
dc.identifier.issn1024-5332-
dc.identifier.pmid12745658-
dc.identifier.doi10.1080/1024533031000084231-
dc.identifier.urihttp://hdl.handle.net/10541/78937-
dc.description.abstractHepatic veno-occlusive disease (VOD) is a common and potentially fatal complication of high dose chemotherapy with allogeneic/autologous stem cell transplant (SCT). The diagnosis and treatment of hepatic VOD is controversial. Clinical features are non-specific and may be mimicked by a number of other conditions causing hyperbilirubinaemia post-transplantation. Plasminogen activator inhibitor-1 (PAI-1) has been proposed as a specific marker of VOD [1]. Defibrotide (DF) is a polydeoxyribonucleotide, which has been found to have anti-thrombotic, anti-ischaemic and thrombolytic properties without causing significant anti-coagulation. Recent evidence [2,3] suggests that use of DF in patients with severe VOD results in a promising response rate without attributable significant toxicity. Between January 1998 and July 1999, PAI-1 levels were measured serially in 16 patients undergoing SCT who had subsequently developed hyperbilirubinaemia. Diagnosis of VOD was made by established clinical criteria [4,5]. At the time of diagnosis, PAI-1 levels (mean+/-SD) were significantly elevated in patients with VOD (90.7+/-47 ng/ml, n=7) when compared with patients with jaundice from other causes post transplantation (12.1+/-6.4 ng/ml, n=9). Five of the patients with VOD received treatment with DF. Four out of five patients showed an initial response to DF (significant fall in bilirubin and improvement in other signs/symptoms) with one of these patients having a complete response (bilirubin < 2.0 mg/dl and full resolution of signs/symptoms and end-organ toxicity). Following treatment with DF, a corresponding fall in PAI-1 levels was noted in those responding, with non-responders maintaining raised levels. Conclusion: Raised PAI-1 levels post stem cell transplant are specific for VOD and a subsequent decrease in levels following treatment with DF may be associated with response to treatment.en
dc.language.isoenen
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBiological Markers-
dc.subject.meshBone Marrow Transplantation-
dc.subject.meshCohort Studies-
dc.subject.meshFemale-
dc.subject.meshFibrinolytic Agents-
dc.subject.meshHepatic Veno-Occlusive Disease-
dc.subject.meshHumans-
dc.subject.meshHyperbilirubinemia-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPlasminogen Activator Inhibitor 1-
dc.subject.meshPolydeoxyribonucleotides-
dc.subject.meshTransplantation Conditioning-
dc.subject.meshTransplantation, Autologous-
dc.subject.meshTransplantation, Homologous-
dc.subject.meshTreatment Outcome-
dc.titleRole of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF).en
dc.typeArticleen
dc.contributor.departmentDepartments of Medical Oncology and Haematology, Christie Hospital, Wilmslow Rd, Manchester, UK.en
dc.identifier.journalHematologyen

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