government site. Concurrently the aforementioned phase III study, an international compassionate use program (CUP) (17), has been implemented, aimed to ensure drug supply to a wider range of transplant centers across the world. The incidence of VOD/SOS is higher in children than in adults (7, 9, 1316, 47), although a retrospective analysis of a large Italian pediatric cohort (47) found a surprisingly very low incidence of VOD/SOS [2% (95% confidence interval, 1.72.5)]. EBMT criteria for severity grading of suspected VOD in adults (A) and in children (B). Ciavarella N, Ettorre C, Schiavoni M, Schonauer S, Cicinelli E, Cagnazzo G. Effectiveness of defibrotide for prophylaxis of deep venous thrombosis in gynecological surgery: a double-blind, placebo-controlled clinical trial. baseline at transplant or others signs of MOD/MOF. Ferr C, de Sanjos S, Lastra CF, Mart F, Mario EL, Sureda A, et al.. Pentoxifylline, ciprofloxacin and prednisone failed to prevent transplant-related toxicities in bone marrow transplant recipients and were associated with an increased incidence of infectious complications. The main difference between the two diagnostic systems is hyperbilirubinemia being mandatory in the Baltimore criteria, which implies longer time waiting for its development or intrinsically more aggressive forms. Takamura H, Nakanuma S, Hayashi H, Tajima H, Kakinoki K, Kitahara M, et al.. Al Beihany A, Al Omar H, Sahovic E, Chaudhri N, Al Mohareb F, et al.. Because magnetic resonance and computed tomography represent the gold standard techniques for focal liver lesions identification, particularly in cancer staging and surveillance, their use is still pivotal in post-HSCT VOD/SOS (42, 54, 55). We evaluated in prospective analysis the usefulness of the pediatric EBMT criteria for VOD diagnosis and their presumable impact on cost effectiveness and patients' outcome. 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. Tissue plasminogen activator and N-acetylcysteine are not recommended for increased bleeding risk and lack of efficacy, respectively (100). official website and that any information you provide is encrypted In this study, VOD/SOS diagnosis was performed according to the EBMT criteria and the primary endpoints were both 100-day survival and 100-day complete response of severe VOD/SOS. Ueno T, Bioulac-Sage P, Balabaud C, Rosenbaum J. Innervation of the sinusoidal wall: regulation of the sinusoidal diameter, Budd-Chiari syndrome and veno-occlusive disease/sinusoidal obstruction syndrome. However, this may represent a problem in patients who develop late onset SOS/VOD in the absence of hyperbilirubinemia, with only weight gain and ascites.6, 7, 24 Therefore, hyperbilirubinemia should no longer be mandatory in late onset SOS/VOD, and the diagnosis of late onset SOS/VOD may be made if patients fulfill a less stringent version of the Baltimore criteria, that is, at least two of the following: bilirubin 2mg/dL, painful hepatomegaly, weight gain>5% or ascites. Mohty M, Labopin M, Lebon D, Berceanu A, Jubert C, Yakoub-Agha I, et al. Mohty M1, Malard F1, Abecassis M2, Aerts E3, Alaskar AS4, Aljurf M5, Arat M6, Bader P7, Baron F8, Bazarbachi A9, Blaise D10, Ciceri F11, N-acetylcysteine for hepatic veno-occlusive disease after allogeneic stem cell transplantation. Modified seattle, Baltimore, and EBMT diagnostic criteria in adults (A) and in children (B). Treatment of hepatic venoocclusive disease with recombinant human tissue plasminogen activator or orthotopic liver transplantation after allogeneic bone marrow transplantation. Transplant-associated thrombotic microangiopathy: theoretical Carreras E, Granena A, Navasa M, Bruguera M, Marco V, Sierra J et al. (2015). Wolf CR, Moll E, Friedberg T, Oesch F, Buchmann A, Kuhlmann WD, et al.. To intervene before the development of end-organ damage and MOD/MOF in SOS/VOD, there is a need for accurate identification of risk factors and biomarkers to identify the subset of patients with a likely severe form of the disease and at imminent risk of deteriorating. Defibrotide doses ranged from 10 to 80 mg/kg, because no specific treatment protocol has been adopted. If patients fulfill two or more criteria in two different categories, they must be classified in the most severe category. By defining these new EBMT diagnostic and severity criteria for SOS/VOD, we aimed at overcoming the lack of specificity and sensitivity of the current criteria. The risk of SOS/VOD onset also depends on the conditioning regimen intensity and the drugs used. Revised diagnosis and severity criteria for sinusoidal obstruction Scrobohaci ML, Drouet L, Monem-Mansi A, Devergie A, Baudin B, D'Agay MF et al. Diagnosis of SOS/VOD is based on clinical criteria, such as the Seattle, Baltimore or recently issued European Society for Blood and Marrow Transplantation criteria, to which hemodynamic and/or ultrasound evidence of SOS were added for the first time. Moscardo F, Sanz GF, de La Rubia J, Jimenez C, Saavedra S, Regadera A et al. However, this feature is difficult to evaluate during the pancytopenic phase after conditioning,24 and lack specificity, given the numerous causes of thrombocytopenia after HCT. Treatment of hepatic venocclusive disease with recombinant human tissue plasminogen activator and heparin in 42 marrow transplant patients. Rather, only situations where the alloreactivity of the transplant is increased, such as with the use of an unrelated or an HLA-mismatched donor, and a non T-cell-depleted graft should be considered as risk factors.25, 26 Of note HLA-haploidentical familial donors are increasingly used27 and while no study specifically address the risk of SOS/VOD in this setting, we suggest that the use of a haploidentical donor could be considered as a risk factor as any HLA-mismatched donor. Before MM thanks Prof JV Melo (University of Adelaide, Australia) for critical reading of the manuscript. Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Arai S et al. JAZZ pharmaceuticals provided an unrestricted educational grant for support for the current study, but did not participate to the discussions, conduct of the work, data/results analyses or manuscript writing or reviewing. Severe hepatocellular injury after hematopoietic cell transplant: incidence, etiology and outcome. Twelve cases of hepatic SOS/VOD, termed Chiari's syndrome due to senecio poisoning, were initially reported in humans by Selzer et al ( Selzer and Parker 1951 ). Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, et al.. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study, Inotuzumab ozogamicin for acute lymphoblastic leukemia. Decreased mortality can be attributed to a better intensive care, to increasing proportion of centers with multidisciplinary teams, to a wider use of risk stratification, to earlier treatment. As a library, NLM provides access to scientific literature. Sinusoidal obstruction syndrome ( SOS ), previously known as veno-occlusive disease ( VOD ), is a distinctive and potentially fatal form of hepatic injury that occurs predominantly, if not only, after drug or toxin exposure. Due to the lack of a consensus definition for TA-TMA, the syndrome's incidence and impact is difficult to quantify [ 2 - 8 ]. Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS) is a rare complication characterized by hepatomegaly, right-upper quadrant pain, jaundice, and ascites, occurring after high-dose chemotherapy, hematopoietic stem cell transplantation (HSCT) and, less commonly, other conditions. Here we summarise new information on pathogenesis of SOS/VOD; identify modifiable and unmodifiable risk factors for disease development; propose novel, contemporary and panel opinion-based diagnostic criteria and an innovative organ-based method of SOS/VOD grading classification; and review current approaches for prophylaxis and treatment of . Introduction of new pediatric EBMT criteria for VOD diagnosis: is it The initial step of VOD/SOS pathogenesis is the injury of sinusoidal endothelium of the liver (Figure 1) leading to loss of endothelial cell cohesions: gaps appear in the endothelial barrier, and red blood cells pass through these gaps and accumulates in the Disse space, causing the detachment of the endothelial cells with downstream embolization of the centrilobular vein and subsequent postsinusoidal obstruction (18). Transjugular intrahepatic portosystemic shunting placement has been reported in few anecdotal cases in literature for the treatment of VOD/SOS, but currently its use is not recommended because of poor outcomes (101). Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome. Federal government websites often end in .gov or .mil. HHS Vulnerability Disclosure, Help Lack of consensus on diagnostic criteria and treatment . HHS Vulnerability Disclosure, Help Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. 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. The incidence of VOD/SOS after transplantation varies substantially from 2 to 60% (6, 7, 12, 13, 16, 47) because of both different setting of patients and transplant procedures and of application of different diagnostic criteria. Effects of defibrotide in patients with chronic deep insufficiency. Pulmonary alveolar hemorrhage occurred in 11.8 and 15.6% of the patients, gastrointestinal bleeding in 7.8 vs. 9.4%, and cerebral hemorrhage in 2.9 vs. 3.1%, respectively, in the experimental and control arms. The onset of VOD/SOS can be either smoldering or disruptive, ranging from mild forms spontaneously resolving within few weeks to severe forms with organ damage and MOD. McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Received 2016 Mar 17; Revised 2016 Mar 30; Accepted 2016 Apr 1. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. The https:// ensures that you are connecting to the Thus, LSM progressively allowed reducing the number of liver biopsies performed in patients with advanced liver disease. The site is secure. Tanikawa S, Mori S, Ohhashi K, Akiyama H, Sasaki T, Kaku H et al. 1Hematology Department, Hpital Saint Antoine, and Universit Pierre & Marie Curie, Paris, France, 2Instituto Portugues de Oncologia, Lisbon, Portugal, 3Department of Haematology, University Hospital Zurich, Zurich, Switzerland, 4King Abdullah International Medical Research Center/King Saud Bin Abdulaziz University for Health Sciences, Department of Oncology, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia, 5King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, 6Sisli Florence Nightingale Hospital, HSCT Unit, Istanbul, Turkey, 7Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt/Main, Germany, 8Department of Hematology, University of Liege, Liege, Belgium, 9Department of Internal Medicine, American University of Beirut, Beirut, Lebanon, 10Blood and Marrow Transplantation Program, Hematology Department, Institut Paoli-Calmettes, Marseille, France, 11Hematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milano, Italy, 12Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany, 13Department of Hematology and Immunology, Hospital Robert Debre, Paris 7-Paris Diderot University, Paris, France, 14Department of Clinical Haematology, Central Manchester Foundation Trust, Manchester, UK, 15HSCT division, National Cancer Center Hospital, Tokyo, Japan, 16Hematology Department, Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France, 17Department of Hematology and Stem Cell Transplantation, St Istvan and St Laszlo Hospital, Budapest 3 Department of Internal Medicine, Semmelweis University, Budapest, Hungary, 18Hematology Department, Groupement Hospitalier Sud, Hospices Civils de Lyon, Universit Claude Bernard Lyon EST, Pierre Bnite, France, 19Hematology and Bone Marrow Transplantation, Chaim Sheba Medical center, Tel-Hashomer, Israel, 20National Stem Cell Transplant Unit (Adults), Department of Haematology, St James's Hospital and Academic Department of Haematology, Trinity College Dublin, Dublin, Ireland, 21Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan, 22Department of Haematology, King's College Hospital, London, UK, 23Department of Pediatrics, St Anna Kinderspital, Vienna, Austria, 25Division of Hematologic Malignancy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, 26Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland, 27Hematology and Stem Cell Transplantation Section, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center and Veterans Affairs Medical Center, Nashville, Tennessee, 28Section of Haematology and Coagulation, Department of Internal Medicine, Sahlgrenska University Hospital, Gteborg Sweden, 29CHU de Lille, LIRIC INSERM U995, universit de Lille2, France, 30Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, 31Josep Carreras Foundation & Leukemia Research Institute, Hematology Department, Hospital Clnic, Barcelona, Spain. Patients in the treatment group received defibrotide (DF) 25 mg/kg per day in four divided intravenous infusions, starting with the initiation of conditioning regimen and continuing for 30 days after transplantation or, if discharged from hospital before 30 days after HSCT, for at least 14 days. Collins PW, Gutteridge CN, O'Driscoll A, Blair S, Jones L, Aitchison R et al. Although HokUS-10 score is easier to apply than the Lassau score, it still has to be adequately validated. Data from these important studies are quite superimposable and further confirmed by a systematic review of the literature, which found out 100-day survival of 41% in patients with MOD and 71% in those without MOD (97). The https:// ensures that you are connecting to the EBMT diagnosis and severity criteria for SOS/VOD. Carreras et al.24,67 reported that haemodynamic studies could not confirm the diagnosis of SOS/VOD diagnosis in 42% of adult patients with only two clinical manifestations listed in the Seattle criteria, compared with only 9% using the Baltimore criteria. In more recent reports, mortality rates are significantly lower: 22 and 35% at 100 days and 5 years, respectively, in the retrospective large Italian pediatric cohort (47), and 49.5% estimated survival at 100 days in the T-IND study (16). Hassan M, Ljungman P, Ringdn O, Hassan Z, Oberg G, Nilsson C, et al.. Salat C, Holler E, Kolb HJ, Reinhardt B, Pihusch R, Wilmanns W et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (Long Version). Decreased hepatic nitric oxide production contributes to the development of rat sinusoidal obstruction syndrome, Deleve LD, Wang X, Tsai J, Kanel G, Strasberg S, Tokes ZA. AC, MS, FBar, ID, FR, and MC wrote sections of the manuscript. Early intervention improves outcome - updated results of a treatment IND (T-IND). Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. In this study, each patient had one or more VOD/SOS risk factor including preexisting hepatic disease, second myeloablative transplant, allogeneic transplant for leukemia beyond second relapse, conditioning with busulfan and melphalan, prior treatment with gemtuzumab ozogamicin or a diagnosis of primary hemophagocytic lymph histiocytosis, adrenoleukodystrophy, or osteopetrosis. There are three different kinds of SOS/VOD risk factors: those directly related to the transplant; those related to the patient's characteristics and underlying disease; and hepatic-related risk factors (Table 1). One of the major challenges in the diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is the lack of sensitive laboratory and imaging studies that can accurately assist in diagnosis, which is very important with regard to the prompt start of appropriate treatment. 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. Strouse C, Zhang Y, Zhang MJ, DiGilio A, Pasquini M, Horowitz MM, et al.. Risk score for the development of veno-occlusive disease after allogeneic hematopoietic cell transplant. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Mahgerefteh SY, Sosna J, Bogot N, Shapira MY, Pappo O, Bloom AI. Main limitations for a wide application of this method are the need of a specific training of the operator, the presence of significant amount of ascites, and a body mass index >30 kgm2. 8600 Rockville Pike Treatment-emergent AEs (in patients who received at least one dose of defibrotide) were more frequent in adults than in children (77.9 and 65.5%, respectively) and in patients with MOD (75.2% overall, 81% in adults, and 70.5% in children). Three hundred twenty-four French patients received defibrotide from July 2014 to October 2018; 40 developed severe VOD/SOS, and 120 after HSCT; overall, 105 patients developed a severe/very severe VOD/SOS (89 after HSCT). Chalandon Y, Roosnek E, Mermillod B, Newton A, Ozsahin H, Wacker P, et al.. Prevention of veno-occlusive disease with defibrotide after allogeneic stem cell transplantation. Suppressor of tumorigenecity-2, angiopoietin-2, L-ficolin, hyaluronic acid and vascular cell adhesion molecule-1 (VCAM1) were found to be biomarkers for diagnosis of SOS/VOD. The development of diagnostic criteria is critical to allow clinicians to identify signs and symptoms of a disease entity, make the correct diagnosis in a prompt and confident manner and ultimately initiate therapy when appropriate (Chao, 2014). This study adopted the VOD/SOS diagnosis criteria, and severe VOD/SOS was defined as a VOD/SOS complicated by MOD. Abbreviations: EBMT=European society for Blood and Marrow Transplantation; MOD=multi-organ dysfunction; MOF=multi-organ failure; SOS=sinusoidal obstruction syndrome; VOD=veno-occlusive disease. Faioni EM, Krachmalnicoff A, Bearman SI, Federici AB, Decarli A, Gianni AM et al. Botti S, Orlando L, Gargiulo G, Cecco VD, Banfi M, Duranti L, et al.. Veno-occlusive disease nurse management: development of a dynamic monitoring tool by the GITMO nursing group. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial. Also, the use of prostaglandin E1 was abandoned because of inconclusive results and excess of toxicity (112114). Hepatic sinusoidal obstruction syndrome caused by herbal medicine: CT and MRI features, MR imaging findings in two patients with hepatic veno-occlusive disease following bone marrow transplantation. Novel ultrasonographic scoring system of sinusoidal obstruction syndrome after hematopoietic stem cell transplantation. Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, et al.. It has been used, even in a pivotal way, in acute myocardial infarction (91), in postthrombolysis reocclusion of coronary (92), ischemic damage of the liver (93), diabetic microangiopathy, and Reynaud phenomenon (94). Utility of transvenous liver biopsies and wedged hepatic venous pressure measurements in sixty marrow transplant recipients. The updated EBMT criteria for diagnosis of SOS/VOD in adult patients are given in Table 2. In addition, particular attention should be paid to the number of SOS/VOD risk factors. Kaleelrahman M, Eaton JD, Leeming D, Bowyer K, Taberner D, Chang J et al. Transplant centers adhering to the CUP program enrolled patients developing severe VOD/SOS either after HSCT or after radiotherapy/chemotherapy. 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. Similarly, advances in imaging techniques may call for an update on the specific variables that should be used for diagnosis and prognosis assessment.23 Finally, while current SOS/VOD definitions apply to both adults and children, the clinical presentation of this complication differs between these two patient populations. Corticosteroids, which have been used both in adult (98) and pediatric (99) setting, achieved the 2C level of recommendation in British guidelines (100); their use should be cautiously considered because of the increased risk of infections. Of note, weight increase must be assessed when patients have received an optimal diuretic treatment. McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M et al. Bearman SI, Anderson GL, Mori M, Hinds MS, Shulman HM, McDonald GB. 1, 38, 70 Therefore, it appears to be a relevant parameter for evaluation of SOS/VOD severity. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution's three decade experience. official website and that any information you provide is encrypted Prediction of veno-occlusive disease using biomarkers of endothelial injury. Currently, once the diagnosis of SOS/VOD is established, we lack a score to truly assess its severity, and to identify patients requiring early therapeutic intervention. Treatment includes supportive care, intensive treatment, and specific drug therapy. Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Srivastava A, Poonkuzhali B, Shaji RV, George B, Mathews V, Chandy M et al. Colecchia A, Marasco G, Ravaioli F, Kleinschmidt K, Masetti R, Prete A, et al.. The nurse group of the Italian Society of Bone Marrow Transplantation elaborated an operational flowchart for a dynamic nursing monitoring of patients with suspected or proven VOD/SOS (82). Based on these results, the British Committee for Standards in Hematology and the British Society for Blood and Marrow Transplantation guidelines recommend the use of defibrotide for VOD/SOS prophylaxis in children undergoing HSCT with at least one risk factor for VOD/SOS (evidence IA) (100). Both adult and pediatric criteria have been associated to severity grading scales that are related to the dynamic changes, mainly the evolution of hepatic and renal function tests (Table 2). This is also observed in patients with advanced diseases (beyond CR2 or relapse) and in those with thalassemia.1, 8, 10 Risk factors specific to the pediatric setting are not discussed here (primarily hemophagocytic lymphohistiocytosis, osteopetrosis or thalassemia major, auto-HCT in patients with neuroblastoma, younger age (under 12 years of age) and low weight).1, Hepatic dysfunction before transplant, with increased levels of bilirubin and transaminase, is one of the main risk factors of SOS/VOD.8, 17, 38 This level of dysfunction can be found in preexisting liver disease, such as cirrhosis, fibrosis and active viral hepatitis, or as a result of previous abdominal or hepatic irradiation, or the use of hepatotoxic drugs such as gemtuzumab ozogamicin or inotuzumab ozogamicin.8, 17, 39, 40 Finally, elevated ferritin level and iron overload are also considered as SOS/VOD risk factors.41, 42. Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: incidence, risk factors, and outcome. Bethesda, MD 20894, Web Policies The .gov means its official. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen. The third study was a prospective open-label, single-arm study in an expanded access program (16) enrolling, from 2007 to 2016, patients with hepatic VOD/SOS, both post-HSCT and non-HSCT treatments, with the aim to evaluate 100-day overall survival (primary endpoint) and safety of defibrotide given at the dose of 25 mg/kg for at least 21 days. Glutathione S-transferase M1 polymorphism: a risk factor for hepatic venoocclusive disease in bone marrow transplantation. Sinusoidal obstruction syndrome (SOS), previously known as hepatic veno-occlusive disease (VOD), is a condition arising from occlusion of hepatic venules. PDF Management of Hepatic Veno-occlusive Disease (VOD) Unfractionated heparin and low-molecular-weight heparin have been extensively studied, including some randomized trials, but with inconclusive results (12, 104108). An official website of the United States government. Risk factors associated with the onset of VOD and diagnostic tools have been recently updated both in the pediatric and adult settings and here are reported. Weight increase is part of the diagnostic criteria of SOS/VOD and also reflects the development of ascites. The main limitation consists in being an invasive procedure. Recently, the Center for International Blood and Marrow Transplant Research developed a risk score built on a large population series of more than 13,000 patients (81). Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D et al. Likewise, new risk factors, related to these changes of HCT practice, have been identified and should be taken into account for prognosis assessment. Supportive care and clinical monitoring are primary issues in the management of VOD/SOS throughout the whole HSCT course, in order to promptly capture clinical diagnostic criteria, to timely record all dynamic changes and to follow both the response to treatment and disease progression. In case of no response and progression of VOD/SOS, the prognosis is dismal, and few further treatments are available, with limited efficacy. Jones RJ, Lee KS, Beschorner WE, Vogel VG, Grochow LB, Braine HG, et al.. Venoocclusive disease of the liver following bone marrow transplantation. Dignan F, Gujral D, Ethell M, Evans S, Treleaven J, Morgan G, et al.. Prophylactic defibrotide in allogeneic stem cell transplantation: minimal morbidity and zero mortality from veno-occlusive disease. Bearman SI, Anderson GL, Mori M, Hinds MS, Shulman HM, McDonald GB. We evaluated in prospective analysis the usefulness of the. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT), The role of the endothelium in the short-term complications of hematopoietic SCT. Severe veno-occlusive disease/sinusoidal obstruction syndrome after deceased-donor and living-donor liver transplantation. Nishida M, Kahata K, Hayase E, Shigematsu A, Sato M, Kudo Y, et al.. On retrospective review, 49% of transplant events met either MS and/or EBMT criteria, however, were not diagnosed with SOS/VOD (cohort 2); remaining 38% of transplant events did not meet MS or EBMT criteria and were not diagnosed with SOS/VOD (cohort 3). Imran H, Tleyjeh IM, Zirakzadeh A, Rodriguez V, Khan SP. 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. At present, the available data are too preliminary to conclusively identify a specific form of GvHD prophylaxis as a SOS/VOD risk factor. Diagnosis of VOD/SOS is currently based mainly on clinical criteria; biomarkers for VOD/SOS diagnosis are not yet validated. In addition, patients with MOD/MOF will be systematically classified as very severe.5, 11, 12, 13, 24 This is defined as a clinical syndrome characterized by the development of progressive and potentially reversible physiologic dysfunction in two or more organs.77 Within the proposed new EBMT criteria, renal failure is defined as creatinemia 2 times the baseline at transplant, or creatinine clearance 50% level at transplant, or dialysis; pulmonary failure as oxygen saturation 90% on room air and/or the need for positive pressure/ventilator dependence not attributable to any other cause; central nervous system failure as confusion, lethargy and/or delirium not attributable to any other cause.24. It is well established that serum bilirubin levels increase with the severity of SOS/VOD.17, 24, 70, 72 Therefore, serum bilirubin level cutoff points have been defined to reflect this correlation. The authors did not include pretransplant therapies impacting on VOD/SOS, so the applicability of this model to patient receiving either gemtuzumab ozogamicin or inotuzumab ozogamicin is still unknown. Up to 30% of children with VOD/SOS was anicteric (7, 45, 46) compared to 12% of adults.