title: Hepatic veno-occlusive disease: a chemotherapy-related toxicity in children with malignancies.
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.
authors.affiliation: Division of Paediatric Oncology, Catholic University of Rome, Rome, Italy.
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Cefalo
authors.forename: Palma
authors.initials: P
authors.lastname: Maurizi
authors.forename: Annalisa
authors.initials: A
authors.lastname: Arlotta
authors.forename: Maria
authors.initials: M
authors.lastname: Scalzone
authors.forename: Giorgio
authors.initials: G
authors.lastname: Attinà
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruggiero
authors.forename: Riccardo
authors.initials: R
authors.lastname: Riccardi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D000970:Antineoplastic Agents
references.citation: Eur J Cancer. 1997 Mar;33(3):409-18; discussion 19-20
references.pmid: 9155525
references.citation: Blood. 1998 Nov 15;92(10):3599-604
references.pmid: 9808553
references.citation: Eur J Cancer. 1998 Jul;34(8):1145-7
references.pmid: 9849471
references.citation: J Pediatr Hematol Oncol. 2004 Dec;26(12):843-6
references.pmid: 15591910
references.citation: Blood. 1993 Jun 15;81(12):3458-62
references.pmid: 8507881
references.citation: World J Gastroenterol. 2007 Apr 7;13(13):1912-27
references.pmid: 17461490
references.citation: Eur J Haematol. 2000 May;64(5):281-91
references.pmid: 10863974
references.citation: Blood. 1998 Aug 1;92(3):737-44
references.pmid: 9680339
references.citation: Br J Haematol. 2000 Dec;111(4):1122-9
references.pmid: 11167751
references.citation: Clin Cancer Res. 2000 Feb;6(2):531-5
references.pmid: 10690535
references.citation: Transplantation. 1985 Jun;39(6):603-8
references.pmid: 3890288
references.citation: J Hematother Stem Cell Res. 2002 Apr;11(2):215-29
references.pmid: 11983095
references.citation: Biol Blood Marrow Transplant. 2009 Feb;15(2):231-41
references.pmid: 19167683
references.citation: Bone Marrow Transplant. 2006 Oct;38(8):547-53
references.pmid: 16953210
references.citation: Eur J Pediatr. 1999 Dec;158 Suppl 3:S154-8
references.pmid: 10650858
references.citation: Eur J Cancer. 1997 Nov;33(13):2230-4; discussion 2234-6
references.pmid: 9470811
references.citation: Eur J Cancer. 1998 Jul;34(8):1220-3
references.pmid: 9849483
references.citation: Kobe J Med Sci. 2005;51(3-4):55-65
references.pmid: 16444097
references.citation: Ai Zheng. 2008 Jun;27(6):646-9
references.pmid: 18570742
references.citation: Blood. 2002 Dec 15;100(13):4337-43
references.pmid: 12393437
references.citation: Am J Hematol. 2000 May;64(1):32-8
references.pmid: 10815785
references.citation: J Clin Oncol. 1993 Feb;11(2):304-13
references.pmid: 8426208
references.citation: Curr Opin Hematol. 2003 Nov;10(6):451-62
references.pmid: 14564177
references.citation: Blood. 1998 Dec 15;92(12):4568-72
references.pmid: 9845522
references.citation: Pediatr Blood Cancer. 2006 Apr;46(4):521-3
references.pmid: 16317738
references.citation: Bone Marrow Transplant. 2008 Feb;41(3):229-37
references.pmid: 17994121
references.citation: Med Pediatr Oncol. 1997 Oct;29(4):245-51
references.pmid: 9251728
references.citation: Bone Marrow Transplant. 2007 Jul;40(1):79-82
references.pmid: 17502897
references.citation: Bone Marrow Transplant. 1992 Aug;10(2):135-41
references.pmid: 1525602
references.citation: Pharmacoepidemiol Drug Saf. 2008 Feb;17(2):135-43
references.pmid: 17952879
references.citation: Semin Liver Dis. 2002 Feb;22(1):27-42
references.pmid: 11928077
references.citation: Clin Imaging. 2009 Jul-Aug;33(4):253-60
references.pmid: 19559346
references.citation: Intern Med. 2009;48(10):831-5
references.pmid: 19443980
references.citation: Pediatr Blood Cancer. 2008 Apr;50(4):831-2
references.pmid: 18286502
references.citation: Bone Marrow Transplant. 1996 Jun;17(6):1101-4
references.pmid: 8807121
references.citation: Blood. 2006 Jan 1;107(1):132-4
references.pmid: 16160004
references.citation: Int J Radiat Oncol Biol Phys. 1988 May;14(5):879-84
references.pmid: 3283084
references.citation: Pediatr Hematol Oncol. 2003 Jun;20(4):345-9
references.pmid: 12746168
references.citation: Thromb Haemost. 2005 Apr;93(4):682-9
references.pmid: 15841312
references.citation: Blood. 1992 May 15;79(10):2784-8
references.pmid: 1586725
references.citation: Blood Coagul Fibrinolysis. 2008 Apr;19(3):203-7
references.pmid: 18388499
references.citation: Haematologica. 2005 Oct;90(10):1396-404
references.pmid: 16219577
references.citation: Bone Marrow Transplant. 2003 Jun;31(12):1143-9
references.pmid: 12796794
references.citation: Bone Marrow Transplant. 2004 Aug;34(3):277-8
references.pmid: 15170162
references.citation: Clin Pharmacol Ther. 2006 Oct;80(4):375-83
references.pmid: 17015055
references.citation: Pediatr Transplant. 2007 Feb;11(1):49-57
references.pmid: 17239123
references.citation: Bone Marrow Transplant. 1998 Jun;21(11):1125-30
references.pmid: 9645575
references.citation: Bone Marrow Transplant. 1992 Sep;10(3):197-214
references.pmid: 1422475
references.citation: Med Pediatr Oncol. 1999 Nov;33(5):462-9
references.pmid: 10531570
references.citation: Transplantation. 1987 Dec;44(6):778-83
references.pmid: 3321587
references.citation: Am J Med. 1980 Feb;68(2):285-90
references.pmid: 6986767
references.citation: Gut. 2006 Dec;55(12):1789-94
references.pmid: 16636018
references.citation: Rinsho Ketsueki. 2000 Feb;41(2):103-8
references.pmid: 10723238
references.citation: Pediatr Neonatol. 2008 Aug;49(4):141-4
references.pmid: 19054920
references.citation: Leukemia. 2003 Jun;17(6):1150-6
references.pmid: 12764383
references.citation: Best Pract Res Clin Haematol. 2008 Jun;21(2):149-64
references.pmid: 18503983
references.citation: Gastroenterology. 1980 Dec;79(6):1178-91
references.pmid: 7002704
references.citation: Biol Blood Marrow Transplant. 2004 May;10(5):347-54
references.pmid: 15111934
references.citation: Leukemia. 2003 Aug;17(8):1636-42
references.pmid: 12886253
references.citation: Blood Rev. 2003 Jun;17(2):63-70
references.pmid: 12642120
references.citation: J Pediatr. 1971 Oct;79(4):708-9
references.pmid: 4328654
references.citation: Thromb Res. 2005;116(3):233-40
references.pmid: 15935832
references.citation: Bone Marrow Transplant. 1991;7 Suppl 2:53
references.pmid: 1878718
references.citation: Arch Pathol. 1969 Mar;87(3):279-89
references.pmid: 4974825
references.citation: J Clin Oncol. 1991 Jul;9(7):1224-32
references.pmid: 2045863
references.citation: Haematologica. 2006 Jun;91(6):795-800
references.pmid: 16769582
references.citation: Cancer. 1988 Jul 15;62(2):270-3
references.pmid: 2838151
references.citation: Bone Marrow Transplant. 2002 Jan;29(2):137-43
references.pmid: 11850708
references.citation: Srp Arh Celok Lek. 2010 Jan;138 Suppl 1:33-8
references.pmid: 20229680
references.citation: Eur J Pediatr Surg. 2000 Oct;10(5):300-3
references.pmid: 11194540
references.citation: S Afr Med J. 1979 Jan 6;55(1):5-10
references.pmid: 371033
references.citation: Ann Intern Med. 1993 Feb 15;118(4):255-67
references.pmid: 8420443
references.citation: Transplantation. 2002 Jul 15;74(1):60-6
references.pmid: 12134100
references.citation: Blood. 1997 Mar 1;89(5):1501-6
references.pmid: 9057629
references.citation: Fundam Clin Pharmacol. 2008 Dec;22(6):605-8
references.pmid: 19049662
references.citation: J Ultrasound Med. 2003 Oct;22(10):1103-6
references.pmid: 14606568
references.citation: J Clin Oncol. 1993 Sep;11(9):1729-36
references.pmid: 8355040
references.citation: Eur J Haematol. 1991 Nov;47(5):346-54
references.pmid: 1761121
references.citation: Blood. 1995 Jun 1;85(11):3005-20
references.pmid: 7756636
references.citation: Bone Marrow Transplant. 1998 Dec;22(12):1191-7
references.pmid: 9894723
references.citation: Hepatology. 1994 May;19(5):1171-81
references.pmid: 8175139
references.citation: Cancer. 1997 Jun 15;79(12):2435-9
references.pmid: 9191535
references.citation: Dig Liver Dis. 2007 Feb;39(2):105-16
references.pmid: 17196894
references.citation: J Korean Med Sci. 2006 Oct;21(5):897-903
references.pmid: 17043426
references.citation: Hepatology. 1984 Jan-Feb;4(1):116-22
references.pmid: 6363247
references.citation: Bone Marrow Transplant. 1999 Dec;24(12):1311-4
references.pmid: 10627640
references.citation: Hepatology. 1986 May-Jun;6(3):450-6
references.pmid: 3086205
references.citation: Blood. 1994 May 1;83(9):2723-30
references.pmid: 8167351
references.citation: Hematology. 2003 Apr;8(2):91-5
references.pmid: 12745658