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Successful treatment of sinusoidal obstructive syndrome after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin

Bone Marrow Transplantation volume 45, pages 783–785 (2010)Cite this article

Hepatic sinusoidal obstructive syndrome (SOS), formerly known as veno-occlusive disease (VOD), is a clinical syndrome characterized by tender hepatomegaly, jaundice, ascites, fluid retention, unexplained weight gain and transfusion refractory thrombocytopenia.1 SOS usually occurs within the first 3 weeks after high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT).1, 2 SOS develops in 5–60% of patients after HSCT and is recognized as one of the most common and important regimen-related toxicities, given the high mortality rate.2 The etiology of VOD remains to be fully elucidated, but is thought to involve injury to sinusoidal endothelial cells by toxic insults such as cytotoxic chemotherapy, resulting in a hypercoagulable state and exaggerated cytokine production.3 An animal model of hepatic SOS has shown that chemotherapy causes a loss of endothelial fenestrations, the formation of gaps in the vascular lining and extravasation of red cells into the space of Disse, resulting in sinusoidal obstruction.3 In addition, endothelial cell damage induces expression of tissue factor, which activates factor VIIa accompanied by downregulation of thrombomodulin, leading to hypercoagulation, as evidenced by deficiencies in the natural anticoagulants protein C and antithrombin (AT)III.1, 2, 3

Recently, ATIII concentrate has been shown to be effective in the treatment of SOS after HSCT, but efficacy as a single agent remains controversial.4 Other promising new agents for SOS include defibrotide, a mixture of single-stranded polydeoxyribonucleotides that possesses local antithrombotic, anti-ischemic and anti-inflammatory activities.5 In multiinstitutional phase II trials involving patients with severe SOS, defibrotide produced 100-day survival rates of 35–45%, compared to 10–20% for best available therapy.5, 6

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Acknowledgements

This work was supported in part by Kochi University President's Discretionary Grant.

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  1. Department of Hematology and Respiratory Medicine, Kochi University, Nankoku, Kochi, Japan

    T Ikezoe, K Togitani, N Komatsu, M Isaka & A Yokoyama

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  1. T Ikezoe
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Correspondence to T Ikezoe.

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Ikezoe, T., Togitani, K., Komatsu, N. et al. Successful treatment of sinusoidal obstructive syndrome after hematopoietic stem cell transplantation with recombinant human soluble thrombomodulin. Bone Marrow Transplant 45, 783–785 (2010). https://doi.org/10.1038/bmt.2009.217

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