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Signs of Progression

Be alert for signs of renal or pulmonary dysfunctionBe prepared to act on VOD/SOS

Signs and symptoms of multi-organ dysfunction may be predictive of VOD/SOS progression and poor survival1,2

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Early onset1-3

Signs and symptoms such as weight gain, hepatomegaly, and elevated bilirubin may appear early and worsen quickly post HSCT

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Rapid worsening2

Short time from the first clinical symptoms to the date of VOD/SOS diagnosis

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High magnitude of severity1,2,4

Symptoms of severe liver dysfunction and extreme elevation in liver lab values

Approximately 30% to 50% of cases developed multi-organ dysfunction5,a

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Renal dysfunction may include3,6,7

  • Decreased urinary output
  • Elevated creatinine levels (≥1.5 x baseline)
  • Decreased creatinine clearance
  • Decreased glomerular filtration rate
  • Need for dialysis
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Pulmonary dysfunction may include1,3,7,8

  • Pulmonary infiltrates
  • Pleural effusion
  • Reduced oxygen saturation
  • Need for supplemental oxygen (nasal cannula)
  • Ventilator dependence

As VOD/SOS progresses to hepatorenal dysfunction, reversal of portal venous outflow may occur; this change in portal circulation is a late-stage finding of VOD/SOS9,10,11

84% overall mortality in VOD/SOS with multi-organ dysfunction12,b

  1. Based on a study conducted by Carreras et al that used 2 sets of diagnostic criteria to estimate the incidence of VOD/SOS after HSCT.5
  2. Based on 19 studies (235 patients) that specifically determined mortality from severe VOD/SOS, as reported within a meta-analysis of 135 studies performed between 1979 and 2007.12

VOD/SOS can rapidly progress to renal or pulmonary dysfunction1,2,13

Average time of onset of symptoms in VOD/SOS post HSCT2

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Study design: Time of onset of VOD/SOS and multi-organ failure is based on 190 patients from a prospective cohort evaluation of 355 consecutive patients. A diagnosis of VOD/SOS was made based on the occurrence of 2 of the following events within 20 days of transplantation: bilirubin >2 mg/dL, hepatomegaly or right upper quadrant pain of hepatic origin, and sudden weight gain (>2% of baseline weight). No other explanation for these signs and symptoms could be present at the time of diagnosis.1,2

HSCT=hematopoietic stem-cell transplantation; SD=standard deviation; SOS-sinusoidal obstruction syndrome; VOD=veno-occlusive disease.

References: 1. 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(4):255-267. 2. Bearman SI. The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood. 1995;85(11):3005-3020. 3. Mohty M, Malard F, Abecassis M, et al. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2016;51(7):906-912. 4. Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2018;53(2):138-145. 5. Carreras E, Díaz-Beyá M, Rosiñol L, et al. 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(11):1713-1720. 6. Ng CK, Chan MH, Tai MH, et al. Hepatorenal syndrome. Clin Biochem Rev. 2007;28(1):11-17. 7. Richardson PG, Riches ML, Kernan NA, et al. Blood. 2016;127(13):1656-1665. 8. Richardson PG, Murakami C, Jin Z, et al. Blood. 2002;100(13):4337-4343. 9. Richardson PG, Ho VT, Cutler C, et al. 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(suppl 1):S88-S90. 10. Carreras E. Early complications after HSCT. In: Apperley J, Carreras E, Gluckman E, et al, eds. The EBMT Handbook. 6th ed. Paris, France: European School of Haematology; 2012:176-195. 11. Cairo MS, Cooke KR, Lazarus HM, Chao N. Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation. Br J Haematol. 2020;190(6):822-836. 12. Coppell JA, Richardson PG, Soiffer R, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16(2):157-168. 13. Carreras E. How I manage sinusoidal obstruction syndrome after haematopoietic cell transplantation. Br J Haematol. 2015;168(4):481-491.