UNLABELLED: 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.
UNLABELLED: 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.
Authors: Corey Cutler; Haesook T Kim; Shaké Ayanian; Gary Bradwin; Carolyn Revta; Julie Aldridge; Vincent Ho; Edwin Alyea; John Koreth; Philippe Armand; Robert Soiffer; Jerome Ritz; Paul G Richardson; Joseph H Antin Journal: Biol Blood Marrow Transplant Date: 2010-02-23 Impact factor: 5.742
Authors: Christian Schoergenhofer; Nina Buchtele; Georg Gelbenegger; Ulla Derhaschnig; Christa Firbas; Katarina D Kovacevic; Michael Schwameis; Philipp Wohlfarth; Werner Rabitsch; Bernd Jilma Journal: Sci Rep Date: 2019-07-31 Impact factor: 4.379
Authors: M Mohty; F Malard; M Abecassis; E Aerts; A S Alaskar; M Aljurf; M Arat; P Bader; F Baron; A Bazarbachi; D Blaise; F Ciceri; S Corbacioglu; J-H Dalle; F Dignan; T Fukuda; A Huynh; T Masszi; M Michallet; A Nagler; M NiChonghaile; S Okamoto; A Pagliuca; C Peters; F B Petersen; P G Richardson; T Ruutu; B N Savani; E Wallhult; I Yakoub-Agha; R F Duarte; E Carreras Journal: Bone Marrow Transplant Date: 2016-05-16 Impact factor: 5.483