Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT)

M Mohty, F Malard, M Abecassis, E Aerts, A S Alaskar, M Aljurf, M Arat, P Bader, F Baron, A Bazarbachi, D Blaise, F Ciceri, S Corbacioglu, J-H Dalle, R F Duarte, T Fukuda, A Huynh, T Masszi, M Michallet, A Nagler, M NiChonghaile, T Pagluica, C Peters, F B Petersen, P G Richardson, T Ruutu, B N Savani, E Wallhult, I Yakoub-Agha, E Carreras, M Mohty, F Malard, M Abecassis, E Aerts, A S Alaskar, M Aljurf, M Arat, P Bader, F Baron, A Bazarbachi, D Blaise, F Ciceri, S Corbacioglu, J-H Dalle, R F Duarte, T Fukuda, A Huynh, T Masszi, M Michallet, A Nagler, M NiChonghaile, T Pagluica, C Peters, F B Petersen, P G Richardson, T Ruutu, B N Savani, E Wallhult, I Yakoub-Agha, E Carreras

Abstract

Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.

Figures

Figure 1
Figure 1
Schematic representation of the hepatic acinus. In sinusoidal obstruction syndrome, obstruction of the hepatic sinusoids occurs in the zone 3 of the hepatic acinus.
Figure 2
Figure 2
Sinusoidal obstruction syndrome pathogenesis. (a) Normal hepatic sinusoid; (b) sinusoidal endothelial cells damaged during conditioning round up favoring the appearance of gaps in the sinusoidal barrier; (c) RBCs, leucocytes and cellular debris penetrate into the space of Disse detaching the endothelial lining; (d) the sloughed sinusoidal lining cells embolize downstream and obstruct the sinusoidal flow (sinusoidal obstruction syndrome). Adapted from 'The role of the endothelium in the short-term complications of hematopoietic SCT' by E Carreras and M Diaz-Ricart.

References

    1. Carreras E. Veno-occlusive disease of the liver after hemopoietic cell transplantation. Eur J Haematol. 2000;64:281–291.
    1. Carreras E, Diaz-Ricart M. The role of the endothelium in the short-term complications of hematopoietic SCT. Bone Marrow Transplant. 2011;46:1495–1502.
    1. 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;4:116–122.
    1. 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;44:778–783.
    1. 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;16:157–168.
    1. 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;92:3599–3604.
    1. 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;17:1713–1720.
    1. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol. 2014;168:481–491.
    1. Eissner G, Multhoff G, Holler E. Influence of bacterial endotoxin on the allogenicity of human endothelial cells. Bone Marrow Transplant. 1998;21:1286–1288.
    1. Fuste B, Mazzara R, Escolar G, Merino A, Ordinas A, Diaz-Ricart M. Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK. Haematologica. 2004;89:578–585.
    1. Mercanoglu F, Turkmen A, Kocaman O, Pinarbasi B, Dursun M, Selcukbiricik F, et al. Endothelial dysfunction in renal transplant patients is closely related to serum cyclosporine levels. Transplant Proc. 2004;36:1357–1360.
    1. DeLeve LD, Shulman HM, McDonald GB. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease) Semin Liver Dis. 2002;22:27–42.
    1. Palomo M, Diaz-Ricart M, Carbo C, Rovira M, Fernandez-Aviles F, Martine C, et al. Endothelial dysfunction after hematopoietic stem cell transplantation: role of the conditioning regimen and the type of transplantation. Biol Blood Marrow Transplant. 2010;16:985–993.
    1. Palomo M, Diaz-Ricart M, Carbo C, Rovira M, Fernandez-Aviles F, Escolar G, et al. The release of soluble factors contributing to endothelial activation and damage after hematopoietic stem cell transplantation is not limited to the allogeneic setting and involves several pathogenic mechanisms. Biol Blood Marrow Transplant. 2009;15:537–546.
    1. Cooke KR, Jannin A, Ho V. The contribution of endothelial activation and injury to end-organ toxicity following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2008;14:23–32.
    1. Biedermann BC. Vascular endothelium and graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:129–138.
    1. Carmona A, Diaz-Ricart M, Palomo M, Molina P, Pino M, Rovira M, et al. Distinct deleterious effects of cyclosporine and tacrolimus and combined tacrolimus-sirolimus on endothelial cells: protective effect of defibrotide. Biol Blood Marrow Transplant. 2013;19:1439–1445.
    1. DeLeve LD. Cellular target of cyclophosphamide toxicity in the murine liver: role of glutathione and site of metabolic activation. Hepatology. 1996;24:830–837.
    1. Almog S, Kurnik D, Shimoni A, Loebstein R, Hassoun E, Gopher A, et al. Linearity and stability of intravenous busulfan pharmacokinetics and the role of glutathione in busulfan elimination. Biol Blood Marrow Transplant. 2011;17:117–123.
    1. Soiffer RJ, Dear K, Rabinowe SN, Anderson KC, Freedman AS, Murray C, et al. Hepatic dysfunction following T-cell-depleted allogeneic bone marrow transplantation. Transplantation. 1991;52:1014–1019.
    1. Moscardo F, Urbano-Ispizua A, Sanz GF, Brunet S, Caballero D, Vallejo C, et al. Positive selection for CD34+ reduces the incidence and severity of veno-occlusive disease of the liver after HLA-identical sibling allogeneic peripheral blood stem cell transplantation. Exp Hematol. 2003;31:545–550.
    1. Hogan WJ, Maris M, Storer B, Sandmaier BM, Maloney DG, Schoch HG, et al. Hepatic injury after nonmyeloablative conditioning followed by allogeneic hematopoietic cell transplantation: a study of 193 patients. Blood. 2004;103:78–84.
    1. Nagler A, Labopin M, Berger R, Bunjes D, Campos A, Socie G, et al. Allogeneic hematopoietic SCT for adults AML using i.v. BU in the conditioning regimen: outcomes and risk factors for the occurrence of hepatic sinusoidal obstructive syndrome. Bone Marrow Transplant. 2014;49:628–633.
    1. Nagler A, Rocha V, Labopin M, Unal A, Ben Othman T, Campos A, et al. Allogeneic hematopoietic stem-cell transplantation for acute myeloid leukemia in remission: comparison of intravenous busulfan plus cyclophosphamide (Cy) versus total-body irradiation plus Cy as conditioning regimen—a report from the acute leukemia working party of the European group for blood and marrow transplantation. J Clin Oncol. 2013;31:3549–3556.
    1. 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;112:4425–4431.
    1. Hagglund H, Remberger M, Klaesson S, Lonnqvist B, Ljungman P, Ringden O. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood. 1998;92:4568–4572.
    1. Srivastava A, Poonkuzhali B, Shaji RV, George B, Mathews V, Chandy M, et al. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Blood. 2004;104:1574–1577.
    1. Seifert C, Wittig S, Arndt C, Gruhn B. Heparanase polymorphisms: influence on incidence of hepatic sinusoidal obstruction syndrome in children undergoing allogeneic hematopoietic stem cell transplantation. J Cancer Res Clin Oncol. e-pub ahead of print 22 October 2014.
    1. 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;22:883–888.
    1. Bearman SI, Shuhart MC, Hinds MS, McDonald GB. Recombinant human tissue plasminogen activator for the treatment of established severe venocclusive disease of the liver after bone marrow transplantation. Blood. 1992;80:2458–2462.
    1. 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;38:547–553.
    1. 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;90:1396–1404.
    1. 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;40:935–944.
    1. 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;118:255–267.
    1. Wadleigh M, Richardson PG, Zahrieh D, Lee SJ, Cutler C, Ho V, et al. Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation. Blood. 2003;102:1578–1582.
    1. 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;379:1301–1309.
    1. Richardson PG, Ho VT, Cutler C, Glotzbecker B, Antin JH, Soiffer R. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: novel insights to pathogenesis, current status of treatment, and future directions. Biol Blood Marrow Transplant. 2013;19:S88–S90.
    1. 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;11:1729–1736.
    1. 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;163:444–457.
    1. 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;66:77–80.
    1. Mohty M, Malard F, Blaise D, Milpied N, Furst S, Tabrizi R, et al. Reduced-toxicity conditioning with fludarabine, once-daily intravenous busulfan, and antithymocyte globulins prior to allogeneic stem cell transplantation: Results of a multicenter prospective phase 2 trial. Cancer. 2014;121:562–569.
    1. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104:857–864.
    1. Cantoni N, Gerull S, Heim D, Halter J, Bucher C, Buser A, et al. Order of application and liver toxicity in patients given BU and CY containing conditioning regimens for allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011;46:344–349.
    1. 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;37:677–686.
    1. Attal M, Huguet F, Rubie H, Huynh A, Charlet JP, Payen JL, et al. Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial. Blood. 1992;79:2834–2840.
    1. Or R, Nagler A, Shpilberg O, Elad S, Naparstek E, Kapelushnik J, et al. Low molecular weight heparin for the prevention of veno-occlusive disease of the liver in bone marrow transplantation patients. Transplantation. 1996;61:1067–1071.
    1. 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;47:346–354.
    1. 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;128:975–981.
    1. 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;64:32–38.
    1. 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;13:206–217.
    1. Park SH, Lee MH, Lee H, Kim HS, Kim K, Kim WS, 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;29:137–143.
    1. 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;100:1977–1983.
    1. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–2101.
    1. 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;25:987–992.
    1. Kim ID, Egawa H, Marui Y, Kaihara S, Haga H, Lin YW, et al. A successful liver transplantation for refractory hepatic veno-occlusive disease originating from cord blood transplantation. Am J Transplant. 2002;2:796–800.
    1. Richardson PG, Corbacioglu S, Ho VT, Kernan NA, Lehmann L, Maguire C, et al. Drug safety evaluation of defibrotide. Expert Opin Drug Saf. 2013;12:123–136.
    1. 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;16:1005–1017.
    1. Richardson P, Tomblyn M, Kernan N, Brochstein JA, Mineishi S, Termuhlen A, et al. Results of a Phase 3 study utilizing a historical control. Defibrotide (DF) in the treatment of severe hepatic veno-occlusive disease (VOD) with multi-organ failure (MOF) following stem cell transplantation (SCT) ASH Annual Meeting Abstracts. 2009;114:654.
    1. Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Arai S, 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. ASH Annual Meeting Abstracts. 2013;122:700–700.
    1. Malard F, Chevallier P, Guillaume T, Delaunay J, Rialland F, Harousseau JL, et al. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: A single-institution's three decade experience. Biol Blood Marrow Transplant. 2014;20:1217–1223.
    1. Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650.
    1. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23:5675–5687.
    1. Mohty M, Malard F, Blaise D, Milpied N, Socie G, Huynh A, et al. Sequential regimen of clofarabine, cytarabine and reduced intensity conditioning (RIC) prior to allogeneic stem cell transplantation (allo-SCT) for acute myeloid leukemia (AML) in primary treatment failure. Blood. 2014;124:1228–1228.
    1. Dirou S, Malard F, Chambellan A, Chevallier P, Germaud P, Guillaume T, et al. Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT. Bone Marrow Transplant. 2014;49:622–627.
    1. Majhail NS, Lazarus HM, Burns LJ. Iron overload in hematopoietic cell transplantation. Bone Marrow Transplant. 2008;41:997–1003.
    1. Trottier BJ, Burns LJ, DeFor TE, Cooley S, Majhail NS. Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI-measured liver iron content. Blood. 2013;122:1678–1684.
    1. 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;92:737–744.
    1. Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, et al. 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. Blood. 2002;100:4337–4343.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi