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Late Effects



Veno-Occlusive Disease (VOD) and HSCT Related Disease

Veno-occlusive disease (VOD) is also called sinusoidal obstruction syndrome (SOS)

This contributes to irreversible hepatic injury in long-term survivors treated with HSCT.

Veno-occlusive disease most commonly occurs after radiation therapy (RT) and chemotherapy for marrow transplantation.

It is the most critical hepatic toxicity and occurs acutely.

Pathology shows occlusion and obliteration of the central veins of the hepatic lobules, with retrograde congestion and secondary necrosis of hepatocytes.

Risk of developing VOD/SOS ranges from 1% to 54% after HSCT with high mortality rates.

Conditioning therapy associated with VOD:

  • Cyclophosphamide and busulfan (may occur with these medications alone and no RT)
  • Total body irradiation

Due to the high mortality rate of VOD/SOS, there is no way to clearly evaluate the long- term hepato-biliary health in HSCT survivors of this condition.  However, long-term complications of veno-occlusive disease can include hepatic failure and portal hypertension.

Other factors also combine to increase the risk of long-term liver damage after HSCT such as graft-versus-host-disease (GVHD) and chronic viral hepatitis and nodular regenerative hyperplasia.

Siderosis (deposition of iron) is found in approximately 90% of long-term survivors of HSCT. Iron overload results from multiple red cell transfusions and dyserythropoiesis leading to increased iron transport through the intestine. Iron overload may exacerbate the course of viral hepatitis - but how much siderosis contributes to liver disease is unclear.

Chronic GVHD

  • This is the leading cause of non-relapse mortality 2 years post HSCT
  • 80% of individuals with chronic GVHD have liver involvement
  • Also causes cholestasis with elevated bilirubin and alkaline phosphatase
  • Can present as acute hepatitis alone
  • Chronic GVHD associated hepatotoxicity exacerbated by:
    • Immunosuppressive agents
    • Antibiotics
    • Antifungal and antiviral drugs
    • Sedatives
    • Anti-emetics
    • Antipyretics
    • Parenteral nutrition


Chronic liver disease may predispose to early mortality in long-term survivors after HSCT



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