Skip to main content
  • 1205 Accesses

Abstract

Hepatotoxicity in the peri-hematopoietic stem cell transplantation (HSCT) period is relatively common with an incidence of approximately 80%. Because the liver plays such a central role in the metabolism of drugs; elimination of toxins; detoxification of metabolic waste products; synthesis of key proteins, such as albumin and clotting factors; bile production; the storage of vitamins A, D, E, and K; as well as the synthesis, metabolism, and/or storage of carbohydrates, proteins, and fats, liver damage during any phase of HSCT can cause a significant degree of morbidity and mortality. The most common causes of HSCT-related hepatotoxicity that occur during the peri-HSCT period include the chemotherapy and/or irradiation used in conditioning regimens, medications commonly used during the peri-HSCT period (e.g., immunosuppressants and antibiotics), total parental nutrition (TPN), iron overload, and infection/sepsis. The most common hepatic complications during the peri-HSCT period are transaminitis, sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), acute graft versus host disease (GvHD) of the liver, and infections involving the liver. Because infections and acute GvHD are addressed in detail in other chapters (see Chaps. 17 and 18, respectively), this chapter will focus primarily on transaminitis and SOS.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Similar content being viewed by others

References

  1. Grochow LB, Jones RJ, Brundrett RB, Braine HG, Chen TL, Saral R, et al. Pharmacokinetics of busulfan: correlation with veno-occlusive disease in patients undergoing bone marrow transplantation. Cancer Chemother Pharmacol. 1989;25(1):55–61.

    Article  CAS  PubMed  Google Scholar 

  2. Majhail NS, Lazarus HM, Burns LJ. Iron overload in hematopoietic cell transplantation. Bone Marrow Transplant. 2008;41(12):997–1003.

    Article  CAS  PubMed  Google Scholar 

  3. Kushner JP, Porter JP, Olivieri NF. Secondary iron overload. ASH Edu Program Book. 2001;2001(1):47–61.

    Google Scholar 

  4. Angelucci E, Barosi G, Camaschella C, Cappellini MD, Cazzola M, Galanello R, et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders. Haematologica. 2008;93(5):741–52.

    Article  PubMed  Google Scholar 

  5. Jacobi N, Herich L. Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation. Eur J Haematol. 2016;97(4):336–41.

    Article  CAS  PubMed  Google Scholar 

  6. Delea TE, Edelsberg J, Sofrygin O, Thomas SK, Baladi JF, Phatak PD, et al. Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review. Transfusion. 2007;47(10):1919–29.

    Article  CAS  PubMed  Google Scholar 

  7. Kalpatthi R, Peters B, Kane I, Holloman D, Rackoff E, Disco D, et al. Safety and efficacy of high dose intravenous desferrioxamine for reduction of iron overload in sickle cell disease. Pediatr Blood Cancer. 2010;55(7):1338–42.

    Article  PubMed  Google Scholar 

  8. Vichinsky E, El-Beshlawy A, Al Zoebie A, Kamdem A, Koussa S, Chotsampancharoen T, et al. Long-term safety and efficacy of deferasirox in young pediatric patients with transfusional hemosiderosis: Results from a 5-year observational study (ENTRUST). Pediatr Blood Cancer. 2017;64(9):28296163.

    Article  Google Scholar 

  9. Bras G, Berry DM, Gyorgy P. Plants as aetiological factor in veno-occlusive disease of the liver. Lancet. 1957;272(6976):960–2.

    Article  CAS  PubMed  Google Scholar 

  10. Jacobs P, Miller JL, Uys CJ, Dietrich BE. Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukaemia. S Afr Med J. 1979;55(1):5–10.

    CAS  PubMed  Google Scholar 

  11. McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993;118(4):255–67.

    Article  CAS  PubMed  Google Scholar 

  12. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4(1):116–22.

    Article  CAS  PubMed  Google Scholar 

  13. Lee JH, Lee KH, Kim S, Lee JS, Kim WK, Park CJ, et al. Relevance of proteins C and S, antithrombin III, von Willebrand factor, and factor VIII for the development of hepatic veno-occlusive disease in patients undergoing allogeneic bone marrow transplantation: a prospective study. Bone Marrow Transplant. 1998;22(9):883–8.

    Article  CAS  PubMed  Google Scholar 

  14. Shulman HM, Gown AM, Nugent DJ. Hepatic veno-occlusive disease after bone marrow transplantation. Immunohistochemical identification of the material within occluded central venules. Am J Pathol. 1987;127(3):549–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Shulman HM, Hinterberger W. Hepatic veno-occlusive disease—liver toxicity syndrome after bone marrow transplantation. Bone Marrow Transplant. 1992;10(3):197–214.

    CAS  PubMed  Google Scholar 

  16. Bearman SI, Hinds MS, Wolford JL, Petersen FB, Nugent DL, Slichter SJ, et al. A pilot study of continuous infusion heparin for the prevention of hepatic veno-occlusive disease after bone marrow transplantation. Bone Marrow Transplant. 1990;5(6):407–11.

    CAS  PubMed  Google Scholar 

  17. Marsa-Vila L, Gorin NC, Laporte JP, Labopin M, Dupuy-Montbrun MC, Fouillard L, et al. Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. Eur J Haematol. 1991;47(5):346–54.

    Article  CAS  PubMed  Google Scholar 

  18. Reiss U, Cowan M, McMillan A, Horn B. Hepatic venoocclusive disease in blood and bone marrow transplantation in children and young adults: incidence, risk factors, and outcome in a cohort of 241 patients. J Pediatr Hematol Oncol. 2002;24(9):746–50.

    Article  PubMed  Google Scholar 

  19. Rosenthal J, Sender L, Secola R, Killen R, Millerick M, Murphy L, et al. Phase II trial of heparin prophylaxis for veno-occlusive disease of the liver in children undergoing bone marrow transplantation. Bone Marrow Transplant. 1996;18(1):185–91.

    CAS  PubMed  Google Scholar 

  20. Schriber J, Milk B, Shaw D, Christiansen N, Baer M, Slack J, et al. Tissue plasminogen activator (tPA) as therapy for hepatotoxicity following bone marrow transplantation. Bone Marrow Transplant. 1999;24(12):1311–4.

    Article  CAS  PubMed  Google Scholar 

  21. Yoon JH, Min WS, Kim HJ, Kim JH, Shin SH, Yahng SA, et al. Experiences of t-PA use in moderate-to-severe hepatic veno-occlusive disease after hematopoietic SCT: is it still reasonable to use t-PA? Bone Marrow Transplant. 2013;48(12):1562–8.

    Article  CAS  PubMed  Google Scholar 

  22. Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, et al. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 2013;163(4):444–57.

    Article  CAS  PubMed  Google Scholar 

  23. DeLeve LD, Shulman HM, McDonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). Semin Liver Dis. 2002;22(1):27–42.

    Article  PubMed  Google Scholar 

  24. Lee SH, Yoo KH, Sung KW, Koo HH, Kwon YJ, Kwon MM, et al. Hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Bone Marrow Transplant. 2010;45(8):1287–93.

    Article  CAS  PubMed  Google Scholar 

  25. Tabbara IA, Ghazal CD, Ghazal HH. Early drop in protein C and antithrombin III is a predictor for the development of venoocclusive disease in patients undergoing hematopoietic stem cell transplantation. J Hematother. 1996;5(1):79–84.

    Article  CAS  PubMed  Google Scholar 

  26. Kaleelrahman M, Eaton JD, Leeming D, Bowyer K, Taberner D, Chang J, et al. Role of plasminogen activator inhibitor-1 (PAI-1) levels in the diagnosis of BMT-associated hepatic veno-occlusive disease and monitoring of subsequent therapy with defibrotide (DF). Hematology. 2003;8(2):91–5.

    Article  CAS  PubMed  Google Scholar 

  27. Salat C, Holler E, Kolb HJ, Pihusch R, Reinhardt B, Penovici M, et al. The relevance of plasminogen activator inhibitor 1 (PAI-1) as a marker for the diagnosis of hepatic veno-occlusive disease in patients after bone marrow transplantation. Leuk Lymphoma. 1999;33(1–2):25–32.

    Article  CAS  PubMed  Google Scholar 

  28. Pihusch V, Pihusch M, Penovici M, Kolb HJ, Hiller E, Pihusch R. Transforming growth factor beta-1 released from platelets contributes to hypercoagulability in veno-occlusive disease following hematopoetic stem cell transplantation. Thromb Res. 2005;116(3):233–40.

    Article  CAS  PubMed  Google Scholar 

  29. Corbacioglu S, Kernan N, Lehmann L, Brochstein J, Revta C, Grupp S, et al. Defibrotide for the treatment of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Expert Rev Hematol. 2012;5(3):291–302.

    Article  CAS  PubMed  Google Scholar 

  30. Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157–68.

    Article  PubMed  Google Scholar 

  31. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol. 2015;168(4):481–91.

    Article  PubMed  Google Scholar 

  32. Kebriaei P, Wilhelm K, Ravandi F, Brandt M, de Lima M, Ciurea S, et al. Feasibility of allografting in patients with advanced acute lymphoblastic leukemia after salvage therapy with inotuzumab ozogamicin. Clin Lymphoma Myeloma Leuk. 2013;13(3):296–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cesaro S, Pillon M, Talenti E, Toffolutti T, Calore E, Tridello G, et al. A prospective survey on incidence, risk factors and therapy of hepatic veno-occlusive disease in children after hematopoietic stem cell transplantation. Haematologica. 2005;90(10):1396–404.

    PubMed  Google Scholar 

  34. Cheuk DK, Wang P, Lee TL, Chiang AK, Ha SY, Lau YL, et al. Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;40(10):935–44.

    Article  CAS  PubMed  Google Scholar 

  35. Carreras E, Bertz H, Arcese W, Vernant JP, Tomas JF, Hagglund H, et al. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood. 1998;92(10):3599–604.

    CAS  PubMed  Google Scholar 

  36. Barker CC, Butzner JD, Anderson RA, Brant R, Sauve RS. Incidence, survival and risk factors for the development of veno-occlusive disease in pediatric hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2003;32(1):79–87.

    Article  CAS  PubMed  Google Scholar 

  37. Ansari M, Lauzon-Joset JF, Vachon MF, Duval M, Theoret Y, Champagne MA, et al. Influence of GST gene polymorphisms on busulfan pharmacokinetics in children. Bone Marrow Transplant. 2010;45(2):261–7.

    Article  CAS  PubMed  Google Scholar 

  38. de Jonge ME, Huitema AD, Beijnen JH, Rodenhuis S. High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy. Br J Cancer. 2006;94(9):1226–30.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pidala J, Kim J, Anasetti C, Kharfan-Dabaja MA, Nishihori T, Field T, et al. Pharmacokinetic targeting of intravenous busulfan reduces conditioning regimen related toxicity following allogeneic hematopoietic cell transplantation for acute myelogenous leukemia. J Hematol Oncol. 2010;3(1):36.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Bearman SI. Avoiding hepatic veno-occlusive disease: what do we know and where are we going? Bone Marrow Transplant. 2001;27(11):1113–20.

    Article  CAS  PubMed  Google Scholar 

  41. Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22(3):400–9.

    Article  PubMed  Google Scholar 

  42. Cutler C, Stevenson K, Kim HT, Richardson P, Ho VT, Linden E, et al. Sirolimus is associated with veno-occlusive disease of the liver after myeloablative allogeneic stem cell transplantation. Blood. 2008;112(12):4425–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bearman SI, Anderson GL, Mori M, Hinds MS, Shulman HM, McDonald GB. Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. J Clin Oncol. 1993;11(9):1729–36.

    Article  CAS  PubMed  Google Scholar 

  44. Naples JC, Skeens MA, Auletta J, Rangarajan H, Abu-Arja R, Horwitz E, et al. Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children. Bone Marrow Transplant. 2016;51(1):135–7.

    Article  CAS  PubMed  Google Scholar 

  45. Gordon B, Tarantolo S, Ruby E, Stephens L, Lynch J, Kessinger A, et al. Increased platelet transfusion requirement is associated with multiple organ dysfunctions in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 1998;22(10):999–1003.

    Article  CAS  PubMed  Google Scholar 

  46. Rio B, Andreu G, Nicod A, Arrago JP, Dutrillaux F, Samama M, et al. Thrombocytopenia in venocclusive disease after bone marrow transplantation or chemotherapy. Blood. 1986;67(6):1773–6.

    CAS  PubMed  Google Scholar 

  47. Chao N. How I treat sinusoidal obstruction syndrome. Blood. 2014;123(26):4023–6.

    Article  CAS  PubMed  Google Scholar 

  48. Mahgerefteh SY, Sosna J, Bogot N, Shapira MY, Pappo O, Bloom AI. Radiologic imaging and intervention for gastrointestinal and hepatic complications of hematopoietic stem cell transplantation. Radiology. 2011;258(3):660–71.

    Article  PubMed  Google Scholar 

  49. Karlas T, Weber J, Nehring C, Kronenberger R, Tenckhoff H, Mossner J, et al. Value of liver elastography and abdominal ultrasound for detection of complications of allogeneic hemopoietic SCT. Bone Marrow Transplant. 2014;49(6):806–11.

    Article  CAS  PubMed  Google Scholar 

  50. Colecchia A, Marasco G, Ravaioli F, Kleinschmidt K, Masetti R, Prete A, et al. Usefulness of liver stiffness measurement in predicting hepatic veno-occlusive disease development in patients who undergo HSCT. Bone Marrow Transplant. 2017;52(3):494–7.

    Article  CAS  PubMed  Google Scholar 

  51. Cutler C, Kim HT, Ayanian S, Bradwin G, Revta C, Aldridge J, et al. Prediction of veno-occlusive disease using biomarkers of endothelial injury. Biol Blood Marrow Transplant. 2010;16(8):1180–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Akil A, Zhang Q, Mumaw CL, Raiker N, Yu J, Velez de Mendizabal N, et al. Biomarkers for diagnosis and prognosis of sinusoidal obstruction syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21(10):1739–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Carreras E, Granena A, Navasa M, Bruguera M, Marco V, Sierra J, et al. On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease. Ann Hematol. 1993;66(2):77–80.

    Article  CAS  PubMed  Google Scholar 

  54. Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987;44(6):778–83.

    Article  CAS  PubMed  Google Scholar 

  55. Myers KC, Dandoy C, El-Bietar J, Davies SM, Jodele S. Veno-occlusive disease of the liver in the absence of elevation in bilirubin in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21(2):379–81.

    Article  PubMed  Google Scholar 

  56. Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH, et al. Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation. Br J Haematol. 2017;178(1):112–8.

    Article  CAS  PubMed  Google Scholar 

  57. Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117(16):4367–75.

    Article  CAS  PubMed  Google Scholar 

  58. Carreras E, Diaz-Beya M, Rosinol L, Martinez C, Fernandez-Aviles F, Rovira M. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant. 2011;17(11):1713–20.

    Article  PubMed  Google Scholar 

  59. Tay J, Tinmouth A, Fergusson D, Huebsch L, Allan DS. Systematic review of controlled clinical trials on the use of ursodeoxycholic acid for the prevention of hepatic veno-occlusive disease in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007;13(2):206–17.

    Article  CAS  PubMed  Google Scholar 

  60. Essell JH, Schroeder MT, Harman GS, Halvorson R, Lew V, Callander N, et al. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128(12 Pt 1):975–81.

    Article  CAS  PubMed  Google Scholar 

  61. Ohashi K, Tanabe J, Watanabe R, Tanaka T, Sakamaki H, Maruta A, et al. The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation. Am J Hematol. 2000;64(1):32–8.

    Article  CAS  PubMed  Google Scholar 

  62. Ruutu T, Eriksson B, Remes K, Juvonen E, Volin L, Remberger M, et al. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100(6):1977–83.

    Article  CAS  PubMed  Google Scholar 

  63. Imran H, Tleyjeh IM, Zirakzadeh A, Rodriguez V, Khan SP. Use of prophylactic anticoagulation and the risk of hepatic veno-occlusive disease in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis. Bone Marrow Transplant. 2006;37(7):677–86.

    Article  CAS  PubMed  Google Scholar 

  64. Brown SA, Goringe A, Fegan C, Davies SV, Giddings J, Whittaker JA, et al. Parenteral glutamine protects hepatic function during bone marrow transplantation. Bone Marrow Transplant. 1998;22(3):281–4.

    Article  CAS  PubMed  Google Scholar 

  65. Corbacioglu S, Cesaro S, Faraci M, Valteau-Couanet D, Gruhn B, Rovelli A, et al. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomised controlled trial. Lancet. 2012;379(9823):1301–9.

    Article  CAS  PubMed  Google Scholar 

  66. Corbacioglu S, Honig M, Lahr G, Stohr S, Berry G, Friedrich W, et al. Stem cell transplantation in children with infantile osteopetrosis is associated with a high incidence of VOD, which could be prevented with defibrotide. Bone Marrow Transplant. 2006;38(8):547–53.

    Article  CAS  PubMed  Google Scholar 

  67. Haussmann U, Fischer J, Eber S, Scherer F, Seger R, Gungor T. Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy. Haematologica. 2006;91(6):795–800.

    PubMed  Google Scholar 

  68. Kornblum N, Ayyanar K, Benimetskaya L, Richardson P, Iacobelli M, Stein CA. Defibrotide, a polydisperse mixture of single-stranded phosphodiester oligonucleotides with lifesaving activity in severe hepatic veno-occlusive disease: clinical outcomes and potential mechanisms of action. Oligonucleotides. 2006;16(1):105–14.

    Article  CAS  PubMed  Google Scholar 

  69. Cella G, Sbarai A, Mazzaro G, Motta G, Carraro P, Andreozzi GM, et al. Tissue factor pathway inhibitor release induced by defibrotide and heparins. Clin Appl Thromb Hemost. 2001;7(3):225–8.

    Article  CAS  PubMed  Google Scholar 

  70. Falanga A, Vignoli A, Marchetti M, Barbui T. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia. 2003;17(8):1636–42.

    Article  CAS  PubMed  Google Scholar 

  71. Guglielmelli T, Bringhen S, Palumbo A. Update on the use of defibrotide. Expert Opin Biol Ther. 2012;12(3):353–61.

    Article  CAS  PubMed  Google Scholar 

  72. Morabito F, Gentile M, Gay F, Bringhen S, Mazzone C, Vigna E, et al. Insights into defibrotide: an updated review. Expert Opin Biol Ther. 2009;9(6):763–72.

    Article  CAS  PubMed  Google Scholar 

  73. Palomo M, Diaz-Ricart M, Rovira M, Escolar G, Carreras E. Defibrotide prevents the activation of macrovascular and microvascular endothelia caused by soluble factors released to blood by autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(4):497–506.

    Article  CAS  PubMed  Google Scholar 

  74. Pellegatta F, Lu Y, Radaelli A, Zocchi MR, Ferrero E, Chierchia S, et al. Drug-induced in vitro inhibition of neutrophil-endothelial cell adhesion. Br J Pharmacol. 1996;118(3):471–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Richardson PG, Corbacioglu S, Ho VT, Kernan NA, Lehmann L, Maguire C, et al. Drug safety evaluation of defibrotide. Expert Opin Drug Saf. 2013;12(1):123–36.

    Article  CAS  PubMed  Google Scholar 

  76. Zhou Q, Chu X, Ruan C. Defibrotide stimulates expression of thrombomodulin in human endothelial cells. Thromb Haemost. 1994;71(4):507–10.

    CAS  PubMed  Google Scholar 

  77. Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D, et al. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood. 1998;92(3):737–44.

    CAS  PubMed  Google Scholar 

  78. Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, et al. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Biol Blood Marrow Transplant. 2010;16(7):1005–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, et al. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood. 2016;127(13):1656–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Corbacioglu S, Carreras E, Mohty M, Pagliuca A, Boelens JJ, Damaj G, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: final results from the International Compassionate-Use Program. Biol Blood Marrow Transplant. 2016;22(10):1874–82.

    Article  CAS  PubMed  Google Scholar 

  81. Azoulay D, Castaing D, Lemoine A, Hargreaves GM, Bismuth H. Transjugular intrahepatic portosystemic shunt (TIPS) for severe veno-occlusive disease of the liver following bone marrow transplantation. Bone Marrow Transplant. 2000;25(9):987–92.

    Article  CAS  PubMed  Google Scholar 

  82. Barkholt L, Remberger M, Hassan Z, Fransson K, Omazic B, Svahn BM, et al. A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41(9):785–90.

    Article  CAS  PubMed  Google Scholar 

  83. Smith AR, Triplett BM, Kernan NA, Grupp SA, Arai S, Haut PR, et al. Results of the large prospective study on the use of defibrotide (DF) in the treatment of hepatic veno-occlusive disease (VOD) in hematopoietic stem cell transplant (HSCT). Early intervention improves outcome – updated results of a treatment IND (T-IND) expanded access protocol. Blood. 2013;122(21):700.

    Google Scholar 

  84. Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, et al. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015;50(6):781–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Valerie I. Brown MD, PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Brown, V.I. (2018). Hepatotoxicity in the Peri-HSCT Period. In: Brown, V. (eds) Hematopoietic Stem Cell Transplantation for the Pediatric Hematologist/Oncologist. Springer, Cham. https://doi.org/10.1007/978-3-319-63146-2_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-63146-2_15

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-63144-8

  • Online ISBN: 978-3-319-63146-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics