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Defibrotide

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https://www.readbyqxmd.com/read/29350496/venoocclusive-disease-due-to-chemotherapy-for-pediatric-acute-lymphoblastic-leukemia-is-associated-with-increased-levels-of-plasminogen-activator-inhibitor-1
#1
Margherita Mauro, Graziella Saggiorato, Maria Teresa Sartori, Giuseppe Gallo, Massimiliano De Bortoli, Elisa Bonetti, Ada Zaccaron, Virginia Vitale, Rita Balter, Matteo Chinello, Simone Cesaro
We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement...
January 19, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29335623/sinusoidal-obstruction-syndrome-veno-occlusive-disease-after-high-dose-intravenous-busulfan-melphalan-conditioning-therapy-in-high-risk-ewing-sarcoma
#2
Massimo Eraldo Abate, Anna Paioli, Sivlia Cammelli, Marilena Cesari, Alessandra Longhi, Emanuela Palmerini, Stefano Ferrari, Elisa Carretta, Piero Picci, Fabio Piscaglia
This mono-institutional observational study was conducted to determine incidence, severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell transplantation (ASCT). During the past 10 years, 75 consecutive ES patients resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide therapy was started as soon as the medication was available...
January 15, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29333010/sinusoidal-obstruction-syndrome-during-treatment-for-wilms-tumor-a-life-threatening-complication
#3
Sidharth Totadri, Amita Trehan, Deepak Bansal, Richa Jain
Context: Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D) which is indispensable in the management of WT is associated with the development of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. Aims: The aim is to study the presentation, management, and outcome of SOS complicating ACT-D administration in WT. Settings and Design: Retrospective file review conducted in a Pediatric Hematology-Oncology unit...
October 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29326798/late-onset-hepatic-veno-occlusive-disease-after-allografting-report-of-two-cases-with-atypical-clinical-features-successfully-treated-with-defibrotide
#4
Alessia Castellino, Stefano Guidi, Chiara Maria Dellacasa, Antonella Gozzini, Irene Donnini, Chiara Nozzoli, Sara Manetta, Semra Aydin, Luisa Giaccone, Moreno Festuccia, Lucia Brunello, Enrico Maffini, Benedetto Bruno, Ezio David, Alessandro Busca
Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of hematopoietic stem cell transplantation (HSCT). Here we report two patients receiving an allogeneic HSCT who developed late onset VOD with atypical clinical features. The two patients presented with only few risk factors, namely, advanced acute leukemia, a myeloablative busulphan-containing regimen and received grafts from an unrelated donor. The first patient did not experience painful hepatomegaly and weight gain and both patients showed only a mild elevation in total serum bilirubin level...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29304536/defibrotide-stimulates-angiogenesis-and-protects-endothelial-cells-from-calcineurin-inhibitor-induced-apoptosis-via-upregulation-of-akt-bcl-xl
#5
Xiangmin Wang, Bin Pan, Yuko Hashimoto, Hiroshi Ohkawara, Kailin Xu, Lingyu Zeng, Takayuki Ikezoe
Sinusoidal obstruction syndrome is a life-threatening complication that can occur after haematopoietic stem cell transplantation. Defibrotide (DF) has been approved for the treatment of individuals with severe sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in the European Union and the United States. However, the precise mechanisms by which DF protects endothelial cells remain to be elucidated. In this study, we found that DF stimulated angiogenesis in vitro and in vivo as assessed by vascular tube formation, scratch-wound repair and Matrigel plug assays...
January 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29301447/defibrotide-sodium-for-the-treatment-of-hepatic-veno-occlusive-disease-sinusoidal-obstruction-syndrome
#6
Paul G Richardson, Brandon M Triplett, Vincent T Ho, Nelson Chao, Fiona L Dignan, Michelle Maglio, Mohamad Mohty
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered: Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States...
January 5, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29022099/defibrotide-for-the-treatment-of-sinusoidal-obstruction-syndrome-evaluation-of-response-to-therapy-and-patient-outcomes
#7
John Coutsouvelis, Sharon Avery, Michael Dooley, Carl Kirkpatrick, Andrew Spencer
PURPOSE: Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). METHODS: Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines...
October 11, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28993886/thrombotic-microangiopathy-following-haematopoietic-stem-cell-transplant
#8
Eleanor G Seaby, Rodney D Gilbert
Thrombotic microangiopathy is a potentially lethal complication of haematopoietic stem cell (bone marrow) transplantation. The pathophysiology is incompletely understood, although endothelial damage appears to be central. Platelet activation, neutrophil extracellular traps and complement activation appear to play key roles. Diagnosis may be difficult and universally accepted diagnostic criteria are not available. Treatment remains controversial. In some cases, withdrawal of calcineurin inhibitors is adequate...
October 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28939456/combination-of-high-dose-methylprednisolone-and-defibrotide-for-veno-occlusive-disease-in-pediatric-hematopoietic-stem-cell-transplant-recipients
#9
Nicholas J Gloude, Sonata Jodele, Ashley Teusink-Cross, Michael Grimley, Stella M Davies, Adam Lane, Kasiani C Myers
Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for 6 doses) in patients with VOD, showing good success...
September 20, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28914546/defibrotide-an-oligonucleotide-for-sinusoidal-obstruction-syndrome
#10
May T Aziz, Payal P Kakadiya, Samantha M Kush, Kylie Weigel, Denise K Lowe
OBJECTIVE: To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. DATA SOURCES: A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials...
February 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28860002/thrombotic-microangiopathy-after-allogeneic-stem-cell-transplantation-a-comparison-of-eculizumab-therapy-and-conventional-therapy
#11
Stephan R Bohl, Florian Kuchenbauer, Stefanie von Harsdorf, Nadine Kloevekorn, Stefan S Schönsteiner, Arefeh Rouhi, Phyllis Schwarzwälder, Hartmut Döhner, Donald Bunjes, Martin Bommer
We report the results of a single-center analysis of a cohort of 39 patients treated between 1997 and 2016 for transplantion-associated thrombotic microangiopathy. We evaluated 2 subgroups of patients: 24 patients treated between 1997 and 2014 who received conventional therapy and 15 patients treated with the complement-inhibiting monoclonal antibody eculizumab between 2014 and 2016. The conventional therapy group was treated predominantly with defibrotide alone or in combination with plasmapheresis or rituximab...
August 30, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28859028/sinusoidal-obstruction-syndrome-during-chemotherapy-of-pediatric-cancers-and-its-successful-management-with-defibrotide
#12
Hande Kizilocak, Gürcan Dikme, Nihal Özdemir, Sebuh Kuruğoğlu, İbrahim Adaletli, Tülay Erkan, Tiraje Celkan
Sinusoidal obstruction syndrome (SOS) is a life-threatening complication generally occurring after hematopoietic stem cell transplantation. SOS after standard dose chemotherapy in malignancies is rare. Between the year 1995 and 2016, 414 patients were diagnosed with acute lymphoblastic leukemia and 113 patients were diagnosed with Wilms tumor in our institution. Among these patients, 4 patients with acute lymphoblastic leukemia (0.96%) and 2 patients with Wilms tumor (1.7%) developed SOS during treatment. SOS behaves like a local disseminated intravascular coagulation...
October 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28842141/defibrotide-use-in-vincristine-induced-hepatic-sinusoidal-obstruction-syndrome
#13
Catherine Tang, Julian Lindsay, Anthony Gill, Ian Kerridge
No abstract text is available yet for this article.
August 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28825848/defibrotide-for-children-and-adults-with-hepatic-veno-occlusive-disease-post-hematopoietic-cell-transplantation
#14
Selim Corbacioglu, Paul G Richardson
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a complication that is typically associated with conditioning for hematopoietic stem cell transplantation (HSCT). In patients with concomitant multi-organ dysfunction, mortality may be >80%. Recently, the European Society for Blood and Marrow Transplantation established separate criteria for diagnosis and severity of VOD/SOS for adults and children, to better reflect current understanding of the disease. Areas covered: This review provides an overview of post-HSCT hepatic VOD/SOS and defibrotide, including its pharmacological, clinical, and regulatory profile...
October 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28754544/consensus-report-by-pediatric-acute-lung-injury-and-sepsis-investigators-and-pediatric-blood-and-marrow-transplantation-consortium-joint-working-committees-supportive-care-guidelines-for-management-of-veno-occlusive-disease-in-children-and-adolescents-part
#15
REVIEW
Rajinder P S Bajwa, Kris M Mahadeo, Benjamin H Taragin, Christopher C Dvorak, Jennifer McArthur, Asumthia Jeyapalan, Christine N Duncan, Robert Tamburro, Alison Gehred, Leslie Lehman, Paul Richardson, Jeffery J Auletta, Ann E Woolfrey
Veno-occlusive disease (VOD) is a common and potentially fatal complication in children undergoing hematopoietic cell transplantation (HCT). It occurs in about one-third of all patients undergoing transplantation and is fatal in 50% of patients with severe disease. Early intervention and specific treatment with defibrotide are associated with improved outcomes. However, there is a lack of supportive care guidelines for management of the multiorgan dysfunction seen in most cases. There is high variability in the management of VOD, which may contribute to the increased morbidity and mortality...
July 25, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28715896/use-of-abdominal-ultrasound-in-the-diagnosis-of-hepatic-sinusoidal-obstruction-syndrome-sos-in-a-patient-receiving-a-hematopoietic-cell-transplant
#16
Marta Abadía Barnó, Eva Marín Serrano, Gloria Ruiz Fernández
The sinusoidal obstruction syndrome (SOS) is an uncommon form of portal hypertension that occurs in hematopoietic-cell transplant recipients who receive intense conditioning treatments. The diagnosis is clinical and it is usually delayed, because in these patients there are many causes that can damage the liver and can delay its detection. We present the case of a 47-year-old man, whose diagnosis was made with clinical and analytical data supported by ultrasound signs that showed hepatic congestion. After treatment with defibrotide the patient improved clinically and analytically...
July 18, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28504490/additive-effect-of-mesenchymal-stem-cells-and-defibrotide-in-an-arterial-rat-thrombosis-model
#17
Dilek Dilli, Emine Kılıç, Nihat Yumuşak, Serdar Beken, Duygu Uçkan Çetinkaya, Ramazan Karabulut, Ayşegu L Zenciroğlu
BACKGROUND/AIM: In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. METHODS: Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT...
June 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28491036/pharmacological-activity-and-clinical-use-of-pdrn
#18
REVIEW
Francesco Squadrito, Alessandra Bitto, Natasha Irrera, Gabriele Pizzino, Giovanni Pallio, Letteria Minutoli, Domenica Altavilla
PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28460209/low-fixed-dose-defibrotide-in-management-of-hepatic-veno-occlusive-disease-post-stem-cell-transplantation
#19
Bhausaheb Bagal, Arun Chandrasekharan, Aliya Chougle, Navin Khattry
OBJECTIVE/BACKGROUND: Hepatic veno-occlusive disease (VOD) is well recognized potentially serious regimen-related toxicity seen after stem cell transplantation. Severe VOD is associated with poor long-term outcomes with very high mortality. Besides supportive care, only defibrotide has been found to be effective in the management of VOD. The recommended dose of defibrotide is 25mg/kg/d but there has been no classical dose finding study done for this drug. A higher dose of defibrotide is associated with increased risk of bleeding and this drug is prohibitively expensive...
April 25, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28444784/earlier-defibrotide-initiation-post-diagnosis-of-veno-occlusive-disease-sinusoidal-obstruction-syndrome-improves-day-100-survival-following-haematopoietic-stem-cell-transplantation
#20
Paul G Richardson, Angela R Smith, Brandon M Triplett, Nancy A Kernan, Stephan A Grupp, Joseph H Antin, Leslie Lehmann, Maja Miloslavsky, Robin Hume, Alison L Hannah, Bijan Nejadnik, Robert J Soiffer
Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a progressive, potentially fatal complication of conditioning for haematopoietic stem cell transplant (HSCT). The VOD/SOS pathophysiological cascade involves endothelial-cell activation and damage, and a prothrombotic-hypofibrinolytic state. Severe VOD/SOS (typically characterized by multi-organ dysfunction) may be associated with >80% mortality. Defibrotide is approved for treating severe hepatic VOD/SOS post-HSCT in the European Union, and for hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States...
July 2017: British Journal of Haematology
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