Question

On day 20 post-hematopoietic stem cell transplant (HSCT), a child develops jaundice, breathlessness, and difficulty walking. What is the most likely diagnosis?

• A. Late post-engraftment syndrome
• B. Sinusoidal obstruction syndrome (SOS)/Veno-occlusive disease
• C. Budd-Chiari syndrome
• D. Acute GVHD

Hint:

Post-HSCT Day 10--30 Diagnostic Triad:
Jaundice ($\uparrow$ Bilirubin) + Painful Hepatomegaly + Fluid retention Weight gain $\rightarrow$ Sinusoidal Obstruction Syndrome (SOS/VOD). Drug of choice: Defibrotide.

Answer 1

The Correct Option is B

Concept:
Sinusoidal Obstruction Syndrome (SOS), formerly and synonymously termed Hepatic Veno-Occlusive Disease (VOD), is a life-threatening, early endothelial complication following myeloablative conditioning regimens in Hematopoietic Stem Cell Transplantation (HSCT).
Explanation:
• SOS/VOD results from toxic injury to the sinusoidal endothelial cells and hepatocytes in zone 3 of the hepatic acinus caused by high-dose conditioning chemotherapy (e.g., busulfan, cyclophosphamide) or total body irradiation.

• Endothelial cell damage leads to sloughing, subendothelial edema, microvascular thrombosis, and fibrous obliteration of the hepatic terminal venules and sinusoids.

• This produces post-sinusoidal intrahepatic portal hypertension, presenting classically between day $+10$ and day $+30$ post-HSCT with the Seattle/EBMT diagnostic clinical triad:
1. Hyperbilirubinemia progressive jaundice
2. Painful hepatomegaly and right upper quadrant tenderness
3. Rapid fluid retention with unexplained weight gain ($>2\text{--}5\%$), refractory ascites, and peripheral edema.

• Severe ascites and fluid retention lead to abdominal compartment pressure, diaphragmatic splinting (causing breathlessness/tachypnea), and tense lower-extremity edema (causing difficulty walking).

• The approved first-line definitive therapeutic agent is Defibrotide, an oligonucleotide that stabilizes endothelial membranes and restores local thrombo-fibrinolytic balance.

• Acute GVHD presents predominantly with a maculopapular rash, secretory diarrhea, and hyperbilirubinemia, without marked sinusoidal portal hypertensive fluid retention/weight gain.
Final Answer:
The clinical triad of jaundice, sudden weight gain/fluid retention, breathlessness, and edema around day 20 post-HSCT is classic for Sinusoidal Obstruction Syndrome (SOS) Veno-Occlusive Disease.