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

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.

 

References:

  1. Corbacioglu S, Carreras E, Ansari M, Balduzzi A, Cesaro S, Dalle JH, Dignan F, Gibson B, Guengoer T, Gruhn B, Lankester A, Locatelli F, Pagliuca A, Peters C, Richardson PG, Schulz AS, Sedlacek P, Stein J, Sykora KW, Toporski J, Trigoso E, Vetteranta K, Wachowiak J, Wallhult E, Wynn R, Yaniv I, Yesilipek A, Mohty M, Bader P. 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 Feb;53(2):138-145. [Medline]
  2. Colecchia A, Ravaioli F, Sessa M, Alemanni VL, Dajti E, Marasco G, Vestito A, Zagari RM, Barbato F, Arpinati M, Cavo M, Festi D, Bonifazi F. Liver Stiffness Measurement Allows Early Diagnosis of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Adult Patients Who Undergo Hematopoietic Stem Cell Transplantation: Results from a Monocentric Prospective Study. Biol Blood Marrow Transplant. 2019 May;25(5):995-1003. [Medline]

 

 

Created Jun 12, 2019.