Diagnosis and Severity Criteria for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Children

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Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of hematopoietic cell transplantation (HCT) that belongs to a group of diseases increasingly identified as transplant-related, systemic endothelial diseases. In most cases, SOS/VOD resolves within weeks; however, severe SOS/VOD results in multi-organ dysfunction/failure with a mortality rate >80%.

EBMT diagnostic criteria for hepatic SOS/VOD in children

  • No limitation for time of onset of SOS/VOD

The presence of two or more of the followinga

  • Unexplained consumptive and transfusion-refractory thrombocytopeniab
  • Otherwise unexplained weight gain on three consecutive days despite the use of diuretics or a weight gain >5% above baseline value
  • cHepatomegaly (best if confirmed by imaging) above baseline value
  • cAscites (best if confirmed by imaging) above baseline value
  • Rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 h

Abbreviations: CT= computed tomography; HCT= hematopoietic cell transplantation; MRI = magnetic resonance imaging; SOS/VOD= sinusoidal obstruction
syndrome/veno-occlusive disease; US=ultrasonography; EBMT=European Society for Blood and Marrow Transplantation

a With the exclusion of other potential differential diagnoses.
b ≥ 1 weight-adjusted platelet substitution/day to maintain institutional transfusion guidelines.
c Suggested: imaging (US, CT or MRI) immediately before HCT to determine baseline value for both hepatomegaly and ascites.


EBMT criteria for grading the severity of suspected hepatic SOS/VOD in children

CTCAE Mild Moderate Severe Very severe MOD/MOF
1 2 3 4
LFTb (ALT, AST, GLDH) ≤2 × normal >2 and ≤5 × normal >5 >5
Persistent RTb <3 days 3–7 days >7 days >7 days
Bilirubin (mg/dL)b <2 <2 ≥2 ≥2
Bilirubin (μmol/L) <34 <34 ≥34 ≥34
Ascitesb Minimal Moderate Necessity for paracentesis (external drainage)
Bilirubin kinetics Doubling within 48 h
Coagulation Normal Normal Impaired coagulation Impaired coagulation with need for replacement of coagulation factors
Renal function GFR (mL/min) 89–60 59–30 29–15 <15 (renal failure)
Pulmonary function (oxygen requirement) <2 L/min >2 L/min Invasive pulmonary ventilation (including CPAP)
CNS Normal Normal Normal New onset cognitive impairment

Abbreviations: ALT= alanine transaminase; AST= aspartate transaminase; CNS =central nervous system; CPAP=continuous positive airway pressure;
CTCAE =Common Terminology Criteria for Adverse Events; GFR =glomerular filtration rate; GLDH = glutamate dehydrogenase; LFT =liver function test; MOD/
MOF= multi-organ dysfunction/multi-organ failure; RT=refractory thrombocytopenia; SOS/VOD, sinusoidal obstruction syndrome/veno-occlusive disease.

If patient fulfills criteria in different categories they must be classified in the most severe category. In addition, the kinetics of the evolution of cumulative symptoms within 48 h predicts severe disease.

b Presence of ≥ 2 of these criteria qualifies for an upgrade to CTCAE level 4 (very severe SOS/VOD).

c Excluding pre-existent hyperbilirubinemia due to primary disease.



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Created Jun 12, 2019.