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Biol Blood Marrow Transplant. 2019 Feb 21. pii: S1083-8791(19)30143-0. doi: 10.1016/j.bbmt.2019.02.018. [Epub ahead of print]

Risk Factors for Development of and Progression of Hepatic Veno-occlusive Disease/Sinusoidal Obstruction Syndrome.

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Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany. Electronic address:
Department of Leukemia, MD Anderson Cancer Center, Houston, TX.
Department of Hematology and Cell Therapy, Acute Leukemia Working Party EBMT Paris Office, Hôpital Saint-Antoine, Paris, France.


Veno-occlusive disease, also known as sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of allogeneic or autologous hematopoietic stem cell transplantation (HSCT), most commonly associated with high-intensity chemotherapies. Since development of VOD/SOS may be rapid and unpredictable, the importance of identifying risk factors to facilitate prompt diagnosis and timely treatment has become increasingly well recognized. Reporting of new retrospective study data for adults and children and emergence of novel anti-cancer therapies that may increase risk of VOD/SOD also necessitate updates on risk factors, as provided in this review. The latest studies reporting VOD/SOS risk factors support previous data, although the importance of patient-related factors such as acute kidney injury, increased international normalized ratio, female sex (in children), and platelet refractoriness are given greater emphasis in the recent data. Nontransplant-related chemotherapies associated with increased risk for VOD/SOS include oxaliplatin and 5-fluorouracil chemotherapies. The novel antibody-drug conjugates gemtuzumab ozogamicin and inotuzumab ozogamicin are now reported in product labeling to pose risks for VOD/SOS based on clinical trial data; an expert consensus panel has issued recommendations for risk reduction measures with inotuzumab ozogamicin treatment including VOD/SOS prophylaxis and limitation to ≤ 2 inotuzumab ozogamicin treatment cycles. A wide range of biomarkers, including genetic, hematologic, hepatic, and inflammatory factors, as well as novel diagnostic techniques such as thromboelastography and measures of liver stiffness, may further enhance future risk calculation for VOD/SOS, although none have been widely adopted. Continual monitoring and recognition of VOD/SOS risk factors is essential for optimal management of this complication.


Biomarkers; Primary chemotherapy; Risk factors; Veno-occlusive disease/sinusoidal obstruction syndrome; antibody drug conjugates


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