Defibrotide for Hepatic Sinusoidal Obstruction Syndrome in Hematopoietic Stem Cell Transplant

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Hepatic sinusoidal obstruction syndrome is a challenging post-hematopoietic cell transplantation condition to both diagnose and to treat.
Hepatic sinusoidal obstruction syndrome is a challenging post-hematopoietic cell transplantation condition to both diagnose and to treat.

One of the deadliest complications after hematopoietic cell transplantation (HCT) is hepatic sinusoidal obstruction syndrome (HSOS), previously called hepatic veno-occlusive disorder (VOD). Patients with HSOS develop jaundice, right upper quadrant tenderness, hepatomegaly, and new ascites.

Although HSOS is typically seen after HCT, it can occur after a patient receives high dose radiation therapy to the liver, post-chemoembolization of liver tumors, or with chemotherapies such as cyclophosphamide. The pathophysiology of HSOS involves damage to the hepatic endothelial cells, which eventually manifests as occlusion of the hepatic sinusoids and venules.

There are mixed data regarding the exact incidence of HSOS in post-HCT patients. A recent meta-analysis, however, identified a mean incidence of 13.7% amongt 135 studies. This study reported a mortality rate of approximately 84%, with most patients developing multi-organ failure that led to death.1

Most patients will present with HSOS within 3 to 4 weeks post-HCT. There are a multitude of risk factors associated with developing HSOS, including but not limited to older age, pre-existing liver disease (hepatitis B and C), and use of some medications (sirolimus, gemtuzumab, total parenteral nutrition, busulfan, and melphalan.)2,3

There are not many treatments available for patients with severe HSOS. Defibrotide is an intravenous medication approved by the U.S. Food and Drug Administration for the treatment of HSOS using a dose of 6.25 mg/kg every 6 hours for at least 21 days.4 If the patient is still symptomatic and deemed to have HSOS at day 21, the medication can be continued for a maximum of 60 days, or until the symptoms and laboratory values normalize.

Although many of the clinical studies supporting the use of defibrotide in HSOS are limited by the number of patients enrolled, there are several studies supporting its use. The largest study published included 102 patients with HSOS, and showed increased rates of survival (38% versus 25%) and resolution of symptoms (26% versus 13%) at 100 days post-HCT among patients treated with defibrotide, in contrast with controls.5

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