Defibrotide for Sinusoidal Obstruction Syndrome and Nodular Regenerative Hyperplasia After Oxaliplatin-Based Hepatic Intra-Arterial Chemotherapy: A Case Report

Published:October 16, 2021DOI:

      Clinical Practice Points

      • Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of oxaliplatin-based chemotherapy.
      • Nodular regenerative hyperplasia can be associated at a late stage of SOS, and should be suspected in case of signs of portal hypertension such as thrombocytopenia or splenomegaly.
      • To our knowledge, this is the first report of SOS occurring after oxaliplatin hepatic arterial infusion (HAI).
      • We report a case of a 43-year-old man, with colorectal liver metastases with SOS associated with nodular regenerative hyperplasia, diagnosed after 28 cycles of oxaliplatin-based HAI, treated with defibrotide but with a fatal outcome.


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        • Rubbia-Brandt L
        • Audard V
        • Sartoretti P
        • et al.
        Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.
        Ann Oncol. 2004; 15: 460-466
        • Rubbia-Brandt L
        • Lauwers GY
        • Wang H
        • et al.
        Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis.
        Histopathology. 2010; 56: 430-439
        • DeLeve LD
        • Shulman HM
        • McDonald GB
        Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease).
        Semin Liver Dis. 2002; 22: 27-42
        • Puente A
        • Fortea JI
        • Del Pozo C
        • et al.
        Porto-sinusoidal vascular disease associated to oxaliplatin: an entity to think about it.
        Cells. 2019; 8: 1506
        • de Lédinghen V
        • Villate A
        • Robin M
        • et al.
        Sinusoidal obstruction syndrome.
        Clin Res Hepatol Gastroenterol. 2020; 44: 480-485
        • Tajima H
        • Ohta T
        • Miyashita T
        • et al.
        Oxaliplatin-based chemotherapy induces extravasated platelet aggregation in the liver.
        Mol Clin Oncol. 2015; 3: 555-558
        • Miyata T
        • Takamura H
        • Kin R
        • et al.
        Spleen volume as a predictive biomarker for thrombocytopenia and liver dysfunction after oxaliplatin-based chemotherapy.
        Anticancer Res. 2020; 40: 3361-3370
        • Chapelle N
        • Matysiak-Budnik T
        • Douane F
        • Metairie S
        • Rougier P
        • Touchefeu Y
        Hepatic arterial infusion in the management of colorectal cancer liver metastasis: current and future perspectives.
        Dig Liver Dis. 2018; 50: 220-225
        • Dzodic R
        • Gomez-Abuin G
        • Rougier P
        • et al.
        Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model.
        Anticancer Drugs. 2004; 15: 647-650
        • González Vicent M
        • Díaz de Heredia C
        • González de Pablo J
        • et al.
        Defibrotide in hematopoietic stem cell transplantation: a multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).
        Eur J Haematol. 2021; 106: 842-850
        • Kernan NA
        • Grupp S
        • Smith AR
        • et al.
        Final results from a defibrotide treatment-IND study for patients with hepatic veno-occlusive disease/sinusoidal obstruction syndrome.
        Br J Haematol. 2018; 181: 816-827
        • Lim A
        • Le Sourd S
        • Senellart H
        • et al.
        Hepatic arterial infusion chemotherapy for unresectable liver metastases of colorectal cancer: a multicenter retrospective study.
        Clin Colorectal Cancer. 2017; 16: 308-315
        • Lévi FA
        • Boige V
        • Hebbar M
        • et al.
        Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV.
        Ann Oncol. 2016; 27: 267-274
        • Ducreux M
        • Ychou M
        • Laplanche A
        • et al.
        Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer.
        J Clin Oncol. 2005; 23: 4881-4887
        • Tamandl D
        • Klinger M
        • Eipeldauer S
        • et al.
        Sinusoidal obstruction syndrome impairs long-term outcome of colorectal liver metastases treated with resection after neoadjuvant chemotherapy.
        Ann Surg Oncol. 2011; 18: 421-430
        • Morris-Stiff G
        • White AD
        • Gomez D
        • et al.
        Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.
        Eur J Surg Oncol. 2014; 40: 1016-1020
        • Ranieri G
        • Laforgia M
        • Nardulli P
        • et al.
        Oxaliplatin-based intra-arterial chemotherapy in colo-rectal cancer liver metastases: a review from pharmacology to clinical application.
        Cancers (Basel). 2019; 11: 141
        • Richardson P
        • Aggarwal S
        • Topaloglu O
        • Villa KF
        • Corbacioglu S
        Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS).
        Bone Marrow Transplant. 2019; 54: 1951-1962
        • Hisaka T
        • Ishikawa H
        • Sakai H
        • et al.
        Sinusoidal obstruction syndrome and postoperative complications resulting from preoperative chemotherapy for colorectal cancer liver metastasis.
        Anticancer Res. 2019; 39: 4549-4554
        • Overman MJ
        • Ferrarotto R
        • Raghav K
        • et al.
        The addition of bevacizumab to oxaliplatin-based chemotherapy: impact upon hepatic sinusoidal injury and thrombocytopenia.
        J Natl Cancer Inst. 2018; 110: 888-894