Restricted accessReview articleFirst published online 2016-6
Prophylaxis and treatment recommendations for sinusoidal obstruction syndrome in adult and pediatric patients undergoing hematopoietic stem cell transplant: a review of the literature
Sinusoidal obstruction syndrome, a complication occurring early after hematopoietic stem cell transplantation, is a concern for clinicians. There are no guidelines to direct clinicians on the optimal way to prevent and treat this disease. Newer data show that defibrotide is a promising drug both for prevention and treatment, although it is not yet FDA approved.
BearmanS. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood1995; 85: 3005–3020.
2.
CarrerasEDiaz-BeyaMRosinolL. 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 Transplant2011; 17: 1713–1720.
3.
CarrerasE. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol2015; 168: 481–491.
4.
BianchiGBaroneDLanzarottiE. Defibrotide, a single-stranded polydeoxyribonucleotide acting as an adenosine receptor agonist. Eur J Pharmacol1993; 238: 327–334.
5.
EchartCLGraziadioBSomainiS. The fibrinolytic mechanism of defibrotide: effect of defibrotide on plasmin activity. Blood Coagul Fibrinolysis2009; 20: 627–634.
6.
OatesJAGarretAFitzGeraldGA. Clinical implications of prostaglandin and thromboxane A2 formation. N Engl J Med1988; 319: 689–698 and 761–767.
7.
ChalandonYRoosnekEMermillodB. Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation. Biol of Blood Marrow Transplant2004; 10: 347–354.
8.
DignanFGujralDEthellM. Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. Bone Marrow Transplant2007; 40: 79–82.
9.
SakaiMStrasserSShulmanH. Severe hepatocellular injury after hematopoietic cell transplant: incidence, etiology, and outcome. Bone Marrow Transplant2009; 44: 441–447.
10.
CorbaciogluSCesaroSFaraciM. Defibrotide for prophylaxis of hepatic veno-occlusive disease in paediatric haemopoietic stem-cell transplantation: an open-label, phase 3, randomized controlled trial. Lancet2012; 379: 1301–1309.
11.
KowdleyKV. Ursodeoxycholic acid therapy in hepatobiliary disease. Am J Med2000; 108: 481–486.
12.
EssellJHThompsonJMHarmanGS. Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. Bone Marrow Transplant1992; 10: 367–372.
13.
EssellJHSchroederMTHarmanGS. Ursodiol prophylaxis against hepatic complications of allogeneic bone marrow transplantation. Ann Intern Med1998; 128: 975–981.
14.
OhashiKTanabeJWatanabeR. The Japanese multicenter open randomized trial of ursodeoxycholic acid prophylaxis for hepatic veno-occlusive disease after stem cell transplantation. Am J Hematol2000; 64: 32–38.
15.
RuutuTErikssonBRemesK. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood2002; 100: 1977–1983.
16.
ParkSHLeeMHLeeH. A randomized trial of heparin plus ursodiol vs heparin alone to prevent hepatic veno-occlusive disease after hematopoietic stem cell transplantation. Bone Marrow Transplant2002; 29: 137–143.
17.
AttalMHuguetFRubieH. Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial. Blood1992; 11: 2834–2840.
18.
ImranHTleyjehIMZirakzadehA. 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 Transplant2006; 27: 677–686.
19.
SjooFAschanJBarkholtL. N-acetyl-L-cysteine does not affect the pharmacokinetics or myelosuppressive effect of busulfan during conditioning prior to allogeneic stem cell transplantation. Bone Marrow Transplantation2003; 32: 349–354.
20.
BarkholtLRembergerMHassanZ. A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant2008; 41: 785–790.
21.
GluckmanEJolivetIScrobohaciML. Use of prostaglandin E1 for prevention of liver veno-occlusive disease in leukaemic patients treated by allogeneic bone marrow transplantation. Br J Haematol1990; 74: 277–281.
22.
BearmanSlShenDDHindsMS. A phase I/II study of prostaglandin E1 for the prevention of hepatic venocclusive disease after bone marrow transplantation. Br J Haematol1993; 84: 724–730.
23.
RichardsonPEliasAKrishnanA. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood1998; 92: 737–744.
24.
ChopraREatonJDGrassiA. Defibrotide for the treatment of hepatic veno-occlusive disease: results of the European compassionate-use study. British J Haematol2000; 111: 1122–1129.
25.
BearmanSAndersonGLMorinM. Venoocclusive disease of the liver: development of a model for predicting fatal outcome after marrow transplantation. J Clin Oncol1993; 11: 1729–1736.
26.
RichardsonPGMurakamiCJinZ. 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 high-risk population and factors predictive of outcome. Blood2002; 100: 4337–4343.
27.
Richardson PG, Tomblyn M, Kernan N, et al. Defibrotide (DF) in the treatment of severe hepatic veno-occlusive disease (SOS) with multi-organ failure (MOF) following stem cell transplantation (SCT): results of a phase 3 study utilizing a historical control. Blood (ASH annual meeting abstract) 2009; 114: abstract 654.
28.
Richardson PG, Smith A, Arai S, Grupp S, Kernan NA, Adams R, et al. Defibrotide (DF) in the treatment of severe hepatic veno-occlusive disease (SOS) with multi-organ failure (MOF): results of a treatment IND expanded access protocol. Blood 2010; 116: abstract 906.
29.
Richardson PG, Steinbach G, Kernan N, et al. Meta-analysis of defibrotide (DF) in the treatment of severe hepatic veno-occlusive disease (SOS) with multi-organ failure (MOF) with comparison to a historical control (HC). Blood (ASH Annual Meeting Abstracts) 2010; 116: Abstract 3481.
30.
CorbaciogluSGreilJPetersC. Defibrotide in the treatment of children with veno-occlusive disease (SOS): a retrospective multicenter study demonstrates therapeutic efficacy upon early intervention. Bone Marrow Transplant2004; 33: 189–195.
31.
SucakGTAkiZSYagciM. Treatment of sinusoidal obstruction syndrome with defibrotide: a single center experience. Transplant Proc2007; 29: 1558–1563.
32.
BulleySRStrahmBDoyleJ. Defibrotide for the treatment of hepatic veno-occlusive disease in children. Pediatr Blood Cancer2007; 48: 700–704.
33.
Corbacioglu S, Carreras E, Mohty M, et al. Defibrotide for the treatment of hepatic veno-occlusive disease: an update from the international compassionate use program in 710 patients. In: ASBMT, San Diego, CA 11 February–15 February 2015, abstract no. 109, pp.S108.New York: Elsevier.
34.
Richardson P, Smith A, Triplett B, et al. Updated results from the ongoing US treatment IND study using defibrotide for patients with hepatic veno-occlusive disease. In: ASBMT, San Diego, CA 11 February–15 February 2015, abstract no. 111, pp.S109. New York: Elsevier.
35.
Richardson P, Kernan N, Grupp S, et al. Defibrotide for the treatment of severe hepatic veno-occlusive disease: an analysis of clinical benefit as determined by number needed to treat (NNT) to achieve complete response and to improve survival. In: ASBMT, San Diego, CA 11 February–15 February 2015, abstract no. 112, pp.S110. New York: Elsevier.
36.
RingdenOWennbergLEriczonBG. Alteplase for hepatic veno-occlusive disease after bone marrow transplantation. Lancet1992; 340: 546–547.
37.
LeaheyAMBuninNJ. Recombinant human tissue plasminogen activator for the treatment of severe hepatic veno-occlusive disease in pediatric bone marrow transplant patients. Bone Marrow Transplant1996; 17: 1101–1104.
38.
BearmanSLeeJLBaronAE. Treatment of hepatic venocclusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients. Blood1997; 89: 1501–1506.
39.
Goyal RK, Wall DA, Yu LC, et al. Identification of patients with hepatic venoocclusive disease likely to respond to rtPA therapy. Blood 199d; 10 (Suppl 1): 632a (abstract).
40.
SchriberJMilkBShawD. Tissue plasminogen activator (tPA) as therapy for hepatotoxicity following bone marrow transplantation. Bone Marrow Transplant1992; 24: 1311–1314.
41.
JonesRJLeeKSBeschornerWE. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation1987; 44: 778–783.
42.
YoonJHMinWSKimHJ. 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 Transplant2013; 48: 1562–1568.
43.
MorrisJDHarrisREHashmiR. Antithrombin-III for the treatment of chemotherapy-induced organ dysfunction following bone marrow transplantation. Bone Marrow Transplant1997; 20: 871–878.
44.
TabbaraIAGhazalCDGhazalHH. 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 Hematother1996; 5: 79–84.
45.
HaireWDRubyEIStephensLC. A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation. Biol Blood Marrow Transplant1998; 4: 142–150.
46.
PeresEKintzelPDanseyR. Early intervention with antithrombin III therapy to prevent progression of hepatic venoocclusive disease. Blood Coagul Fibrinolysis2008; 19: 203–207.
47.
HaussmannUFischerJEberS. Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy. Haematologica2006; 91: 795–800.
48.
MyersKCLawrenceJMarshRA. High-dose methylprednisolone for veno-occlusive disease of the liver in pediatric hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant2013; 19: 500–503.
49.
Al BeihanyAAl OmarHSahovicE. Successful treatment of hepatic veno-occlusive disease after myeloablative allogeneic hematopoietic stem cell transplantation by early administration of a short course of methylprednisolone. Bone Marrow Transplant2008; 41: 287–291.
50.
SchlegelPGHaberHPBeckJ. Hepatic veno-occlusive disease in pediatric stem cell recipients: successful treatment with continuous infusion of prostaglandin E1 and low-dose heparin. Ann Hematol1998; 67: 37–41.
51.
GoringeAPBrownSO’CallaghanU. Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy. Bone Marrow Transplant1998; 21: 829–832.
52.
RingdenORembergerMLehmannS. N-acetylcysteine for hepatic veno-occlusive disease after allogeneic stem cell transplantation. Bone Marrow Transplant2000; 25: 993–996.
53.
Jazz Pharmaceuticals. Jazz pharmaceuticals initiates rolling NDA submission for defibrotide for the treatment of severe hepatic veno-occlusive disease [Article&ID=1996956], http://investor.jazzpharma.com/phoenix.zhtml?c=210227&p=irol-news (2014, accessed 16 March 2015).
54.
DignanFSynnRHadzicN. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol2013; 162: 444–457.
55.
OrRNaglerAShpilbergO. Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients. Transplantation1996; 61: 1067–1071.
56.
RichardsonPGSoifferRJAntinJH. 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 Transplant2010; 16: 1005–1017.
