Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

Fan, Cathy; Crawford, James M.

doi:10.1016/j.jceh.2014.10.002

Cited by 228 publications

(209 citation statements)

References 144 publications

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“…SOS is a potentially life-threatening liver disorder that is thought to be initiated by injury to SECs (24). We showed that thrombocytopenia and microscopic liver injury consistent with early SOS were similarly seen in monkeys dosed with PF-0259, a nonbinding ADC containing the same linker and payload as gemtuzumab ozogamicin and inotuzumab ozogamicin.…”

Section: Discussionmentioning

confidence: 79%

Liver Microvascular Injury and Thrombocytopenia of Antibody–Calicheamicin Conjugates in Cynomolgus Monkeys—Mechanism and Monitoring

Guffroy

Falahatpisheh

Biddle

et al. 2017

Clinical Cancer Research

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Purpose: Adverse reactions reported in patients treated with antibody-calicheamicin conjugates such as gemtuzumab ozogamicin (Mylotarg) and inotuzumab ozogamicin include thrombocytopenia and sinusoidal obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury, and identify potential safety biomarkers.Experimental Design: Cynomolgus monkeys were dosed intravenously at 6 mg/m 2 /dose once every 3 weeks with a nonbinding antibody-calicheamicin conjugate (PF-0259) containing the same linker-payload as gemtuzumab ozogamicin and inotuzumab ozogamicin. Monkeys were necropsied 48 hours after the first administration (day 3) or 3 weeks after the third administration (day 63).Results: PF-0259 induced acute thrombocytopenia (up to 86% platelet reduction) with nadirs on days 3 to 4. There was no indication of effects on megakaryocytes in bone marrow or activation of platelets in peripheral blood. Microscopic evaluation of liver from animals necropsied on day 3 demonstrated midzonal degeneration and loss of sinusoidal endothelial cells (SECs) associated with marked platelet accumulation in sinusoids. Liver histopathology on day 63 showed variable endothelial recovery and progression to a combination of sinusoidal capillarization and sinusoidal dilation/hepatocellular atrophy, consistent with early SOS. Among biomarkers evaluated, there were early and sustained increases in serum hyaluronic acid (HA) that correlated well with serum aspartate aminotransferase and liver microscopic changes, suggesting that HA may be a sensitive diagnostic marker of the liver microvascular injury.Conclusions: These data support the conclusion that target-independent damage to liver SECs may be responsible for acute thrombocytopenia (through platelet sequestration in liver sinusoids) and development of SOS.

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Section: Discussionmentioning

confidence: 79%

Liver Microvascular Injury and Thrombocytopenia of Antibody–Calicheamicin Conjugates in Cynomolgus Monkeys—Mechanism and Monitoring

Guffroy

Falahatpisheh

Biddle

et al. 2017

Clinical Cancer Research

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“…1 VOD is a rare and life-threatening disease that affects approximately 20% of patients who receive high-dose myeloablative conditioning therapy or HSCT. [2][3][4][5][6] The disease is characterized clinically by increased serum bilirubin, hepatomegaly, fluid retention, and weight gain. 2,7 Its pathophysiology is of complex vascular origin consisting of hepatic venules and sinusoidal endothelial injury.…”

Section: Indicationsmentioning

confidence: 99%

“…4 Typically, mild to moderate cases of VOD are self-limiting and resolve with minimal treatment; however, severe cases are associated with liver failure, hepatorenal syndrome, and multiorgan failure, with a mortality rate as high as 84%. 2,3,6,8 Defibrotide is the only approved drug for the treatment of VOD with renal or pulmonary dysfunction following HSCT; however, patients may also be helped by supportive care, including diuresis, transfusion, renal replacement therapy, and analgesia. 1,8 Experimental approaches to the prevention of VOD include administration of ursodeoxycholic acid, heparin, glutamine, antithrombin III, and prostaglandin E 1 ; however, these methodologies have shown limited efficacy.…”

Section: Indicationsmentioning

confidence: 99%

Defibrotide

Baker

Demaris

2016

Hosp Pharm

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Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. The November 2016 monograph topics are apaziquone, crisaborole, irinotecan liposome, plecanatide, and telotristat. The Safety MUE is on methylnaltrexone PO.

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“…It is commonly seen in patients undergoing Hematopoietic Stem Cell Transplantation (HSCT), chemotherapy for liver metastasis/acute myeloid leukemia, radiation induced liver injury, herbal medications, liver transplantation, and in patients with veno-occlusive disease with immunodeficiency syndrome. 32 HSCT is one of the most common causes of SOS. It was previously thought to occur in up to 60% patients, 33 but the overall incidence is now found to be 13.7%.…”

Section: Correct Answers: B and Dmentioning

confidence: 99%