In a review published in Biology of Blood and Marrow Transplantation, researchers presented novel risk factors for the development and progression of veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), as well as implications for the management of this condition.

VOD/SOS is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). It has recently been observed in infants and children in the nontransplant setting as a result of intensive chemotherapy.

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Traditionally, VOD/SOS was diagnosed using the Baltimore or modified Seattle criteria, which included symptoms, particularly hyperbilirubinemia, starting within 3 weeks of transplantation. However, recent studies have shown that requiring hyperbilirubinemia to establish a diagnosis of VOD/SOS may lead to treatment delay, disease progression, and poorer outcomes.

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Researchers reviewed 10 studies evaluating risk factors for VOD/SOS. Transplant-related risk factors in adults included horse antithymocyte globulin usage, oral busulfan administration, myeloablative or busulfan-thiotepa conditioning regimens, 2 or more HSCTs, and trough tacrolimus levels above 5 ng/mL to 10 ng/mL. In children, the use of busulfan was independently associated with VOD/SOS risk.

Hepatic risk factors in adults included performance status 2 or higher, hepatitis C seropositivity, advanced disease, high pre-HSCT ferritin levels with malignant lymphoma, acute kidney injury, platelet refractoriness, and high international normalized ratio. In children, hepatic risk factors included female sex, age younger than 2 years, and high pre-HSCT ferritin levels.

Treatment with oxaliplatin or 5-fluorouracil was significantly associated with liver lesions in a nontransplant setting. The antibody-drug conjugates gemtuzumab ozogamicin and inotuzumab ozogamicin were also found to be associated with increased VOD/SOS risk. Expert-issued recommendations for inotuzumab ozogamicin included prophylaxis treatment for VOD/SOS, monitoring for symptoms, and limitation of inotuzumab to 2 or fewer doses. Of note, early initiation of defibrotide prophylaxis was correlated with better response.

Prognostic biomarkers have been identified, including genetic, hepatic, hematologic, and inflammatory factors; however, their applicability to clinical practice warrant further research.

Various novel diagnostic techniques have been studied. Thromboelastography may predict thrombotic or bleeding risk in VOD/SOS and thereby guide initiation of defibrotide. Ultrasound techniques may identify signs of liver stiffness that indicate fibrous or venous congestion.

Lastly, the researchers proposed a multifactorial scoring approach for diagnosing VOD/SOS. This method would incorporate independent risk factors and use ultrasound and computed tomography.

Disclosure: Parts of this study were funded by Jazz Pharmaceuticals. For a full list of disclosures, please refer to the original study.


1.     Corbacioglu S, Jabbour EJ, Mohty M. Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome [published online February 21, 2019]. Biol Blood Marrow Transplant. doi: 10.1016/j.bbmt.2019.02.018