SpringerLink
Log in

Hepatic Veno-Occlusive Disease

A Chemotherapy-Related Toxicity in Children with Malignancies

  • Leading Article
  • Published:
Pediatric Drugs Aims and scope Submit manuscript

Abstract

Hepatic veno-occlusive disease (VOD) is a major manifestation of liver toxicity associated with conventional and high-dose chemotherapy in children affected by hematologic malignancies and certain solid tumors. Clinically, patients present with jaundice, painful hepatomegaly, and fluid retention, which may evolve into multi-organ failure, a hallmark of severe disease. The pathogenesis is complex and not completely understood, but the damage to sinusoidal endothelium, typically caused by toxic metabolites released from antineoplastic drugs, is thought to play a crucial role, together with cytokine activation, immune deregulation, and coagulopathy.

Diagnosis is based on clinical criteria supported by characteristic ultrasound findings, with the gold standard investigation being hepatic-venous pressure gradient measurement and biopsy. Several treatment options have been tested; the most convincing approach to date is the use of defibrotide, a novel oligonucleotide with antithrombotic and antiplatelet aggregating properties, as well as endothelial-stabilizing effects. This agent, together with other specific forms of supportive care, has shown efficacy in the treatment of established VOD and promising results in the prevention of VOD in pediatric patients receiving chemotherapy.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Carreras E. Veno-occlusive disease of the liver after hemopoietic cell transplantation. Eur J Haematol 2000 May; 64(5): 281–91

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Jacobs P, Miller JL, Uys CJ, et al. Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukemia. S Afr Med J 1979; 55: 5–10

    PubMed  CAS  Google Scholar 

  4. Woods WG, Dehner LP, Nesbit ME, et al. Fatal veno-occlusive disease of the liver following high dose chemotherapy, irradiation and bone marrow transplantation. Am J Med 1980; 68: 285–90

    Article  PubMed  CAS  Google Scholar 

  5. Shulman HM, McDonald GB. Liver disease after marrow transplantation. In: Sale GB, Shulman HM, editors. The pathology of bone marrow transplantation. New York: Mason, 1984: 104

    Google Scholar 

  6. Richardson PG, Elias AD, Krishnan A, 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: 737–44

    PubMed  CAS  Google Scholar 

  7. Green DM, Finklestein JZ, Norkoul P, et al. Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine: a report of the National Wilms’ Tumor Study. Cancer 1988; 62: 270–3

    Article  PubMed  CAS  Google Scholar 

  8. Ortega JA, Donaldson SS, Maurer HM, et al. Venoocclusive disease of the liver after chemotherapy with vincristine, actinomycin D, and cyclophosphamide for the treatment of rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study Group. Cancer 1997; 79(12): 2435–9

    Article  PubMed  CAS  Google Scholar 

  9. Bearman SI. The syndrome of veno-occlusive disease after marrow transplantation. Blood 1995; 85: 3005–20

    PubMed  CAS  Google Scholar 

  10. Eber SW, Gungor T, Veldman A, et al. Favorable response of pediatric stem cell recipients to human protein C concentrate substitution for veno-occlusive disease. Ped Transplant 2007; 11: 49–57

    Article  CAS  Google Scholar 

  11. Allen JR, Carstens LA, Katagiri GJ. Hepatic veins of monkeys with venoocclusive disease. Arch Pathol 1969; 87: 279–89

    PubMed  CAS  Google Scholar 

  12. Shulman HM, McDonald GB, Matthews D, et al. An analysis of hepatic venoocclusive disease and centrilobular hepatic degeneration following bone marrow transplantation. Gastroenterology 1980; 79: 1178–91

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  14. el Mouehli M, Kauffmann FC. Sublobular distribution of transferases and hydrolases associated with glucuronide, sulfate and glutathione conjugation in human liver. Hepatology 1986; 6: 450–6

    Article  Google Scholar 

  15. Sartori MT, Spiezia L, Cesaro S, et al. Role of fibrinolytic and clotting parameters in the diagnosis of liver veno-occlusive disease after hematopoietic stem cell transplantation in a pediatric population. Thromb Haemost 2005; 93(4): 682–9

    PubMed  CAS  Google Scholar 

  16. Smith LH, Dixon JD, Stringham JR, et al. Pivotal role of PAI-1 in a murine model of hepatic vein thrombosis. Blood 2006; 107(1): 132–4

    Article  PubMed  CAS  Google Scholar 

  17. Pihusch V, Pihusch M, Penovici M, et al. 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  PubMed  CAS  Google Scholar 

  18. Faioni EM, Krachmalnicoff A, Bearman SI, et al. Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venoocclusive disease of the liver. Blood 1993; 81(12): 3458–62

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Schots R, Kaufman L, Van Riet I, et al. Proinflammatory cytokines and their role in the development of major transplant-related complications in the early phase after allogeneic bone marrow transplantation. Leukemia 2003; 17(6): 1150–6

    Article  PubMed  CAS  Google Scholar 

  21. Dickinson AM, Holler E. Polymorphisms of cytokine and innate immunity genes and GVHD. Best Pract Res Clin Haematol 2008; 21(2): 149–64

    Article  PubMed  CAS  Google Scholar 

  22. Petaja J, Pitkanen S, Vettenranta K, et al. Serum tumor marker CA 125 is an early and sensitive indicator of veno-occlusive disease in children undergoing bone marrow transplantation. Clin Cancer Res 2000; 26: 881–6

    Google Scholar 

  23. Bayraktar UD, Seren S, Bayraktar Y. Hepatic venous outflow obstruction: three similar syndromes. World J Gastroenterol 2007; 13(13): 1912–27

    PubMed  Google Scholar 

  24. Shulman HM, Fisher LB, Schoch HG, et al. Venoocclusive disease of the liver after marrow transplantation: histological correlates of clinical signs and symptoms. Hepatology 1994; 19: 1171–80

    Article  PubMed  CAS  Google Scholar 

  25. Jevtić D, Vujić D, Zecević Z, et al. Coagulation disturbances in paediatric patients with hepatic veno-occlusive disease after stem cells transplantation. Srp Arh Celok Lek 2010; 138Suppl. 1: 33–8

    PubMed  Google Scholar 

  26. Coppell JA, Brown SA, Perry DJ. Veno-occlusive disease: cytokines, genetics, and hemostasis. Blood Rev 2003; 17: 63–70

    Article  PubMed  Google Scholar 

  27. McDonald GB, Sharma P, Matthews DE, et al. Veno-occlusive disease after bone marrow transplantation: diagnosis, incidence and predisposing factors. Hepatology 1984; 4: 116–22

    Article  PubMed  CAS  Google Scholar 

  28. Jones RJ, Lee KS, Beschorner WE, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation 1987; 44(6): 778–83

    Article  PubMed  CAS  Google Scholar 

  29. Khoury NJ, Kanj V, Abboud M, et al. Abdominal complications of chemotherapy in pediatric malignancies: imaging findings. Clin Imaging 2009; 33(4): 253–60

    Article  PubMed  Google Scholar 

  30. Ghersin E, Brook OR, Gaitini D, et al. Color Doppler demonstration of segmental portal flow reversal: an early sign of hepatic veno-occlusive disease in an infant. J Ultrasound Med 2003; 22: 1103–6

    PubMed  Google Scholar 

  31. Senzolo M, Burra P, Cholongitas E, et al. The transjugular route: the key hole to the liver world. Dig Liver Dis 2007 39: 105–16

    Article  PubMed  CAS  Google Scholar 

  32. Lassau N, Auperin A, Leclere J, et al. Prognostic value of doppler-ultra-sonography in hepatic veno-occlusive disease. Transplantation 2002; 74: 60–6

    Article  PubMed  Google Scholar 

  33. Cholongitas E, Quaglia A, Samonakis D, et al. Transjugular liver biopsy: how good is it for accurate histological interpretation? Gut 2006; 55: 1789–94

    Article  PubMed  CAS  Google Scholar 

  34. Bearman SI, Anderson GL, Mori M, et al. Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. J Clin Oncol 1993; 9: 1729–36

    Google Scholar 

  35. McDonald GB, Hinds MS, Fisher LD, 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: 255–67

    PubMed  CAS  Google Scholar 

  36. Richardson PG, Murakami C, ** Z. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a highrisk population and factors predictive of outcome. Blood 2002; 100: 4337–43

    Article  PubMed  CAS  Google Scholar 

  37. Nevill TJ, Barnett MJ, Klingemann HG, et al. Regimen-related toxicity of busulfan-cyclophosphamide conditioning regimen in 70 patients undergoing allogeneic bone marrow transplantation. J Clin Oncol 1991; 9: 1224–32

    PubMed  CAS  Google Scholar 

  38. Ganem G, Saint-Marc Girardin MF, Kuentz M, et al. Venoocclusive disease of the liver after allogeneic bone marrow transplantation in man. Int J Rad Oncol Biol Phys 1988; 14: 879–84

    Article  CAS  Google Scholar 

  39. Hagglund H, Remberger M, Klaesson S, et al. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood 1998; 92: 4568–72

    PubMed  CAS  Google Scholar 

  40. Carreras E, Bertz H, Arcese W, 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

    PubMed  CAS  Google Scholar 

  41. Matute-Bello G, McDonald GB, Hinds MS, et al. Association of pulmonary function testing abnormalities and severe veno-occlusive disease of the liver after marrow transplantation. Bone Marrow Transplant 1998; 21: 1125–30

    Article  PubMed  CAS  Google Scholar 

  42. Radich JP, Sanders JE, Buckner CD, et al. Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total-body irradiation-containing regimens. J Clin Oncol 1993; 11(2): 304–13

    PubMed  CAS  Google Scholar 

  43. Ringden O, Ruutu T, Remberger M, et al. A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplantation recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. Blood 1994; 83: 2723–30

    PubMed  CAS  Google Scholar 

  44. Meresse V, Hartmann O, Vassal G, et al. Risk factors for hepatic venoocclusive disease after high-dose busulfan-containing regimens followed by autologous bone marrow transplantation: a study in 136 children. Bone Marrow Transplant 1992; 10: 135–41

    PubMed  CAS  Google Scholar 

  45. Essel JH, Thompson JM, Harman GS. Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide. Blood 1992; 79: 2784

    Google Scholar 

  46. Green DM. Wilms’ tumour. Eur J Cancer 1997; 33: 409–18

    Article  PubMed  CAS  Google Scholar 

  47. Farber S. Soft tissue sarcomas. Eur J Cancer 1997; 33: 2230–4

    Article  Google Scholar 

  48. Sulis ML, Bessmertny O, Granowetter L, et al. Veno-occlusive disease in pediatric patients receiving actinomycin D and vincristine only for the treatment of rhabdomyosarcoma. J Pediatr Hematol Oncol 2004; 26(12): 843–6

    PubMed  Google Scholar 

  49. Davidson A, Pritchard J. Actinomycin D, hepatic toxicity and Wilms’ tumour: a mystery explained? Eur J Cancer 1998; 34(8): 1145–8

    Article  PubMed  CAS  Google Scholar 

  50. Bisogno G, de Kraker J, Weirich A, et al. Veno-occlusive disease of the liver in children treated for Wilms’ tumour. Med Ped Oncol 1997; 29: 245–51

    Article  CAS  Google Scholar 

  51. Green DM, Finkelstein JZ, Norkool P, et al. Severe hepatic toxicity after treatment with single-dose dactinomycin and vincristine. Cancer 1988; 62: 270–3

    Article  PubMed  CAS  Google Scholar 

  52. Pochedly C. Hazard of chemotherapy in congenital Wilms’ tumour. J Peds 1971; 79: 708–9

    Article  CAS  Google Scholar 

  53. Tornesello A, Piciacchia D, Mastrangelo S, et al. Veno-occlusive disease of the liver in right-sided Wilms’ tumours. Eur J Cancer 1998; 34(8): 1220–3

    Article  PubMed  CAS  Google Scholar 

  54. Arai S, Lee LA, Vogelsang GB. A systematic approach to hepatic complications in hematopoietic stem cell transplantation. J Hematother Stem Cell Res 2002; 11(2): 215–29

    Article  PubMed  Google Scholar 

  55. Lennard L, Richards S, Cartwright CS, et al. The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther 2006; 80: 375–83

    Article  PubMed  CAS  Google Scholar 

  56. Elli M, Pinarli FG, Dagdemir A, et al. Veno-occlusive disease of the liver in a child after chemotherapy for brain tumor. Pediatr Blood Cancer 2006; 46(4): 521–3

    Article  PubMed  Google Scholar 

  57. Czauderna P, Katski K, Kowalczyk J. Venoocclusive liver disease (VOD) as a complication of Wilms’ tumour management in the series of consecutive 206 patients. Eur J Pediatr Surg 2000; 10(5): 300–3

    Article  PubMed  CAS  Google Scholar 

  58. McDonald GB, Sharma P, Matthews DE, et al. The clinical course of 53 patients with veno-occlusive disease of the liver after bone marrow transplantation. Transplantation 1985; 39(6): 603–8

    Article  PubMed  CAS  Google Scholar 

  59. Ohashi K, Tanabe J, Watanabe R, 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: 32–8

    Article  PubMed  CAS  Google Scholar 

  60. Khoury H, Adkins D, Trinkaus K, et al. Treatment of hepatic veno-occlusive disease with high-dose corticosteroids: an update on 28 stem cell transplant recipients. Blood 1998; 92: 1132a

    Google Scholar 

  61. Haussmann U, Fischer J, Eber S, et al. 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 

  62. Marsa-Vila L, Gorin NC, La Porte JP, et al. Prophylactic heparin does not prevent liver veno-occlusive disease following autologous bone marrow transplantation. Eur J Haematol 1991; 47(5): 346–52

    Article  PubMed  CAS  Google Scholar 

  63. Forrest DL, Thompson K, Dorcas VG, et al. Low molecular weight heparin for the prevention of hepatic veno-occlusive disease (VOD) after hematopoietic stem cell transplantation: a prospective phase II study. Bone Marrow Transplant 2003; 31(12): 1143–9

    Article  PubMed  CAS  Google Scholar 

  64. Park SH, Lee MH, Lee H, et al. A randomized trial of heparin plus ursodiol vs heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant 2002; 29(2): 137–43

    Article  PubMed  CAS  Google Scholar 

  65. Strasser SI, McDonald SJ, Schoch HG. Severe hepatocellular injury after hematopoietic cell transplant: incidence and etiology in 2136 consecutive patients. Hepatology 2000; 32: 299A

    Article  Google Scholar 

  66. Hasegawa S, Horibe K, Kawabe T, et al. Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors. Bone Marrow Transplant 1998; 22(12): 1191–7

    Article  PubMed  CAS  Google Scholar 

  67. Matsumoto Y, Horiike S, Sakagami J, et al. Early ultrasonographic diagnosis and clinical follow-up of hepatic veno-occlusive disease after allogeneic bone marrow transplantation in a patient with acute lymphoblastic leukemia. Intern Med 2009; 48(10): 831–5

    Article  PubMed  Google Scholar 

  68. Ludwig R, Weirich A, Abel U, et al. Hepatotoxicity in patients treated according to the nephroblastoma trial and study SIOP-9/GPOH. Med Pediatr Oncol 1999; 33(5): 462–9

    Article  PubMed  CAS  Google Scholar 

  69. Brice K, Valerie B, Claire G, et al. Risk-adjusted monitoring ofveno-occlusive disease following Bayesian individualization of busulfan dosage for bone marrow transplantation in paediatrics. Pharmacoepidemiol Drug Saf 2008; 17(2): 135–43

    Article  PubMed  CAS  Google Scholar 

  70. Bleyzac N. The use of pharmacokinetic models in paediatric onco-haematology: effects on clinical outcome through the examples of busulfan and cyclosporine. Fundam Clin Pharmacol 2008; 22(6): 605–8

    Article  PubMed  CAS  Google Scholar 

  71. Bartelink IH, Bredius RG, Belitser SV, et al. Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. Biol Blood Marrow Transplant 2009; 15(2): 231–41

    Article  PubMed  CAS  Google Scholar 

  72. Chalandon Y, Roosnek E, Mermillod B, et al. Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2004; 10: 347–54

    Article  PubMed  CAS  Google Scholar 

  73. Dignan F, Gujral D, Ethell M, et al. Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. Bone Marrow Transplant 2007; 40: 79–82

    Article  PubMed  CAS  Google Scholar 

  74. Corbacioglu S, Honig M, Lahr G, 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: 547–53

    Article  PubMed  CAS  Google Scholar 

  75. Qureshi A, Marshall L, Lancaster D. Defibrotide in the prevention and treatment of veno-occlusive disease in autologous and allogeneic stem cell transplantation in children. Pediatr Blood Cancer 2008; 50(4): 831–2

    Article  PubMed  Google Scholar 

  76. Wadleigh M, Ho V, Momtaz P, et al. Hepatic veno-occlusive disease: pathogenesis, diagnosis and treatment. Curr Opin Hematol 2003; 10: 451–62

    Article  PubMed  Google Scholar 

  77. Strasser SI, McDonald GB. Gastrointestinal and hepatic complications. In: Forman SJ, Blume KG, Thomas ED, editors. Hematopoietic cell transplantation. 2nd ed. Oxford: Blackwell Publishing, 1998

    Google Scholar 

  78. Leahey AM, Bunin NJ. Recombinant human tissue plasminogen activator for the treatment of severe hepatic veno-occlusive disease in pediatric bone marrow transplant patients. Bone Marrow Transplant 1996; 17: 1101–4

    PubMed  CAS  Google Scholar 

  79. Yoshimi A, Kato K, Maeda N, et al. Treatment of hepatic veno-occlusive disease after bone marrow transplantation with recombinant human tissue plasminogen activator (rh-tPA). Rinsho Ketsueki 2000; 41(2): 103–8

    PubMed  CAS  Google Scholar 

  80. Bearman SI, Lee JL, Baron AE, et al. Treatment of hepatic veno-occlusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients. Blood 1997; 89: 1501–6

    PubMed  CAS  Google Scholar 

  81. Mertens R, Brost H, Granzen B, et al. Antithrombin treatment of severe hepatic veno-occlusive disease in children with cancer. Eur J Pediatr 1999; Suppl. 3: 154–8

    Google Scholar 

  82. Peres E, Kintzel P, Dansey R, et al. Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease. Blood Coagul Fibrinolysis 2008; 19(3): 203–7

    Article  PubMed  CAS  Google Scholar 

  83. Ibrahim A, Pico JL, Maraninchi D, et al. Hepatic veno-occlusive disease following bone marrow transplantation treated by prostaglandin E1. Bone Marrow Transplant 1991; 7Suppl. 2: 53

    PubMed  Google Scholar 

  84. Dong M, Lin Q, Wu XY. Efficiency of prevention and treatment of venoocclusive disease of the liver after allogeneic stem cell transplantation. Ai Zheng 2008; 27(6): 646–9

    PubMed  Google Scholar 

  85. Song JS, Seo JJ, Moon HN, et al. Prophylactic low-dose heparin or prostaglandin E1 may prevent severe veno-occlusive disease of the liver after allogeneic hematopoietic stem cell transplantation in Korean children. J Korean Med Sci 2006; 21(5): 897–903

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  87. Chen IL, Yang SN, Hsiao CC, et al. Treatment with high-dose methylprednisolone for hepatic veno-occlusive disease in a child with rhabdomyosarcoma. Pediatr Neonatol 2008; 49(4): 141–4

    Article  PubMed  Google Scholar 

  88. Akyüz C, CaClar K, Emir S, et al. High-dose methylprednisolone treatment of hepatic veno-occlusive disease in a child with Wilms tumor. Pediatr Hematol Oncol 2003; 20(4): 345–9

    PubMed  Google Scholar 

  89. Yakushi** K, Matsui T, Okamura A, et al. Successful treatment with defibrotide for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. Kobe J Med Sci 2005; 51(3–4): 55–65

    PubMed  Google Scholar 

  90. Falanga A, Vignoli A, Marchetti M, et al. Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells. Leukemia 2003; 17: 1636–42

    Article  PubMed  CAS  Google Scholar 

  91. Ho VT, Revta C, Richardson PG. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: update on defibrotide and other current investigational therapies. 2008; 41: 229–37

  92. Chopra R, Eaton JD, Grassi A, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. Br J Haematol 2000; 111: 1122–9

    Article  PubMed  CAS  Google Scholar 

  93. Cesaro S, Pillon M, Talenti E, 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: 1396–404

    PubMed  Google Scholar 

  94. Ammann RA. Defibrotide for hepatic VOD in children: exact statistics can help! Bone Marrow Transplant 2004; 34(3): 277–8

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. Division of Paediatric Oncology, Catholic University of Rome, Rome, Italy

    Maria Giuseppina Cefalo, Palma Maurizi, Annalisa Arlotta, Maria Scalzone, Giorgio Attinà,  Antonio Ruggiero & Riccardo Riccardi

Authors
  1. Maria Giuseppina Cefalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Palma Maurizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Annalisa Arlotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Scalzone
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giorgio Attinà
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Ruggiero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Riccardo Riccardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Ruggiero.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cefalo, M.G., Maurizi, P., Arlotta, A. et al. Hepatic Veno-Occlusive Disease. Pediatr-Drugs 12, 277–284 (2010). https://doi.org/10.2165/11531840-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11531840-000000000-00000

Keywords

Search

Navigation