BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation.
TL;DR: It is suggested that the role of plasminogen activator inhibitor 1 levels remains an area for further research but that these levels should not form part of the routine diagnostic work‐up for VOD (SOS) at present.
Abstract: Summary of Key RecommendationsDiagnosis
It is recommended that the diagnosis of veno-occlusive disease (sinusoidal obstruction syndrome) [VOD (SOS)] be based primarily on established clinical criteria (modified Seattle or Baltimore criteria) (1A).
Ultrasound imaging may be helpful in the exclusion of other disorders in patients with suspected VOD (SOS) (1C).
It is recommended that liver biopsy be reserved for patients in whom the diagnosis of VOD (SOS) is unclear and there is a need to exclude other diagnoses (1C).
It is recommended that liver biopsies are undertaken using the transjugular approach in order to reduce the risks associated with the procedure (1C).
It is suggested that the role of plasminogen activator inhibitor 1 levels remains an area for further research but that these levels should not form part of the routine diagnostic work-up for VOD (SOS) at present (2C).
Risk factors
It is recommended that patients are assessed for risk factors for VOD (SOS) and that these risk factors are addressed prior to haematopoietic stem cell transplantation (1A).
Prophylaxis
Defibrotide is recommended at a dose of 6·25 mg/kg intravenously four times daily for the prevention of VOD (SOS) in children undergoing allogeneic stem cell transplantation with the following risk factors: pre-existing hepatic disease, second myeloablative transplant, allogeneic transplant for leukaemia beyond second relapse, conditioning with busulfan-containing regimens, prior treatment with gemtuzumab ozogamicin, diagnosis of primary haemophagocytic lymphohistiocytosis, adrenoleucodystrophy or osteopetrosis (1A).
Defibrotide is suggested at a dose of 6·25 mg/kg intravenously four times daily for the prevention of VOD (SOS) in adults undergoing allogeneic stem cell transplantation with the following risk factors: pre-existing hepatic disease, second myeloablative transplant, allogeneic transplant for leukaemia beyond second relapse, conditioning with busulfan-containing regimens, prior treatment with gemtuzumab ozogamicin, diagnosis of primary haemophagocytic lymphohistiocytosis, adrenoleucodystrophy or osteopetrosis (2B).
Prostaglandin E1 is not recommended in the prophylaxis of VOD (SOS) due to lack of efficacy and toxicity (1B).
Pentoxifylline is not recommended in the prophylaxis of VOD (SOS) due to lack of efficacy (1A).
Ursodeoxycholic acid is suggested for use in the prophylaxis of VOD (SOS) (2C).
Heparin (unfractionated and low molecular weight) is not suggested for use in the prophylaxis of VOD (SOS) due to the risk of increased toxicity (2B).
Antithrombin is not suggested for the prophylaxis of VOD (SOS) due to lack of efficacy (2B).
Treatment
Defibrotide is recommended in the treatment of VOD (SOS) in adults and children (1B).
Tissue plasminogen activator is not recommended for use in the treatment of VOD (SOS) due to the associated risk of haemorrhage (1B).
N-acetylcysteine is not routinely recommended for use in the treatment of veno-occlusive disease due to lack of efficacy (1A).
Methylprednisolone may be considered for use in the treatment of veno-occlusive disease with the appropriate caveats of caution regarding infection (2C).
Judicious clinical care, particularly in the management of fluid balance, is recommended in the management of VOD (SOS) (1C).
Early discussion with critical care specialists and a specialist hepatology unit is recommended in the management of VOD (SOS) and other treatment options including transjugular intrahepatic portosystemic shunt or hepatic transplantation may be considered (1C).
Summary
A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology (BCSH) and the British Society for Blood and Marrow Transplantation (BSBMT) has reviewed the available literature and made recommendations for the diagnosis and management of veno-occlusive disease of the liver following haematopoietic stem cell transplantation (HSCT). This guideline includes recommendations for both prophylaxis and treatment of the condition and includes recommendations for children and adults undergoing HSCT.
Citations
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508 citations
Instituto Português de Oncologia Francisco Gentil1, University of Zurich2, King Saud bin Abdulaziz University for Health Sciences3, Goethe University Frankfurt4, University of Liège5, American University of Beirut6, University of Regensburg7, Paris Diderot University8, Semmelweis University9, Claude Bernard University Lyon 110, Sheba Medical Center11, Trinity College, Dublin12, Keio University13, University of Cambridge14, LDS Hospital15, Harvard University16, University of Helsinki17, Vanderbilt University18, University of Gothenburg19, Lille University of Science and Technology20, Autonomous University of Madrid21
TL;DR: A new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, are proposed on behalf of the European Society for Blood and Marrow Transplantation.
Abstract: The advances in hematopoietic cell transplantation (HCT) over the last decade have led to a transplant-related mortality below 15%. Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%. A timely diagnosis of SOS/VOD is of critical importance, given the availability of therapeutic options with favorable tolerability. Current diagnostic criteria are used for adults and children. However, over the last decade it has become clear that SOS/VOD is significantly different between the age groups in terms of incidence, genetic predisposition, clinical presentation, prevention, treatment and outcome. Improved understanding of SOS/VOD and the availability of effective treatment questions the use of the Baltimore and Seattle criteria for diagnosing SOS/VOD in children. The aim of this position paper is to propose new diagnostic and severity criteria for SOS/VOD in children on behalf of the European Society for Blood and Marrow Transplantation.
365 citations
University of Zurich1, King Saud bin Abdulaziz University for Health Sciences2, Goethe University Frankfurt3, University of Liège4, American University of Beirut5, University of Regensburg6, Paris Diderot University7, Semmelweis University8, Claude Bernard University Lyon 19, Sheba Medical Center10, Trinity College, Dublin11, University of Cambridge12, LDS Hospital13, Harvard University14, Helsinki University Central Hospital15, Vanderbilt University Medical Center16, Sahlgrenska University Hospital17
TL;DR: This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments.
Abstract: Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
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Cites background from "BCSH/BSBMT guideline: diagnosis and..."
...Defibrotide is the only FDA-approved treatment for SOS and is generally reserved for moderate or severe cases.(246-248) In the past, some authorities have recommended it for prophylaxis in high-risk cases, but the benefit of this approach is unproven, and the acquisition costs for the drug are very high....
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...The suggested dose is 12 mg/kg divided in two doses starting the day before conditioning and continuing for 3 months after HSCT. • Defibrotide is the only FDA-approved treatment for SOS and is recommended for treatment of moderate-to-severe SOS....
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...(245) Thus, ursodeoxycholic acid is recommended as prophylactic therapy for SOS in patients undergoing allogeneic HSCT.(244,246,247) The suggested dose is 12 mg/kg divided in two doses starting the day before conditioning and continuing for 3 months after HSCT. Defibrotide is the only FDA-approved treatment for SOS and is generally reserved for moderate or severe cases....
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...(228) It occurs most commonly as a complication of myeloablative chemotherapy regimens (high-dose with or without total-body irradiation) used before hematopoietic stem cell transplantation (HSCT), particularly following allogeneic (as opposed to autologous) HSCT.(1) Chemotherapeutic agents known to cause SOS are alkylating agents (cyclophosphamide, busulfan, and melphalan) and the platinum complexes (oxaliplatin, carboplatin, and cisplatin)....
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...(245) Thus, ursodeoxycholic acid is recommended as prophylactic therapy for SOS in patients undergoing allogeneic HSCT.(244,246,247) The suggested dose is 12 mg/kg divided in two doses starting the day before conditioning and continuing for 3 months after HSCT....
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References
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01 Jan 2004
TL;DR: The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not candidates for interferons.
Abstract: Although treatment of hepatitis C has improved,up to 50% do not respond to standard therapy with interferonregimes or cannot tolerate the treatment due to side effects.The purpose of the present investigation was to evaluate thesafety and effectiveness of the antiviral drug amantadine forthe treatment of hepatitis C in those who had either previouslyfailed interferon therapy or were not candidates for interferon.
2,865 citations
Journal Article•
2,135 citations
"BCSH/BSBMT guideline: diagnosis and..." refers background in this paper
...The distribution of the histological changes can be patchy and sampling error may be a limiting factor (DeLeve et al, 2009)....
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TL;DR: The clinical impression is that the current incidence of VOD at the institution is much higher than the 21% rate reported 9 years ago and that more patients have severe liver disease, which may explain the apparent increased incidence and severity of this complication.
Abstract: Objective: To determine the incidence and clinical course of veno-occlusive disease of the liver (VOD) after bone marrow transplantation and to analyze risk factors for severe VOD. Design: Cohort s...
1,120 citations
TL;DR: This guideline has been approved by the American Association for the Study of Liver Diseases (AASLD) and represents the position of the association.
859 citations
"BCSH/BSBMT guideline: diagnosis and..." refers background in this paper
...The distribution of the histological changes can be patchy and sampling error may be a limiting factor (DeLeve et al, 2009)....
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TL;DR: VOD is a common complication of bone marrow transplantation and has a specific clinical presentation, which usually allows diagnosis without the need of liver biopsy, and is the third leading cause of death in allogeneic graft recipients, and the second leading cause in patients receiving autologous transplants.
Abstract: Review of 235 consecutive patients undergoing bone marrow transplantation was performed in order to define the clinical syndrome of venoocclusive disease of the liver (VOD) in these patients. Analysis of all patients with histologically proven VOD revealed a consistent clinical syndrome of liver dysfunction occurring within the first 3 weeks after marrow infusion. This was characterized by hyperbilirubinemia peaking at greater than or equal to 2 mg/dl with at least 2 of 3 other findings: hepatomegaly, ascites, and 5% or greater weight gain. VOD developed in 22% (52 of 235). A persistently elevated aspartate aminotransferase (SGOT) prior to transplant was associated with an increased risk of developing VOD by multivariate analysis (P = 0.0003), and acute leukemia in first remission was associated with a decreased risk (P = 0.02). Neither the preparative regimen (busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation) nor the type of graft (allogeneic versus autologous) influenced the occurrence. Twenty-four of these 52 patients (47%) died with VOD (10% of the entire group). This makes VOD the third leading cause of death in our allogeneic graft recipients, and the second leading cause in our patients receiving autologous transplants. VOD is a common complication of bone marrow transplantation and has a specific clinical presentation, which usually allows diagnosis without the need of liver biopsy.
794 citations
"BCSH/BSBMT guideline: diagnosis and..." refers methods in this paper
...The diagnosis of VOD is primarily based on achievement of established clinical criteria including both the Seattle and the Baltimore criteria (McDonald et al, 1984, 1993; Jones et al, 1987)....
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