Veno Occlusive Disease

Veno-occlusive disease (VOD) occurs as a complication of chemotherapy and/or radiation in allogeneic stem cell transplant. It is a common life-threatening complication of preparative-regimen-related toxicity of stem cell transplantation. It occurs after approximately 20% of allogeneic stem cell transplantations and after about 10% of autologous stem cell transplantations. VOD is characterized by fibrous obliteration of small hepatic vessels. It usually occurs within the first 30 days.

Clinical Manifestations

• Hepatomegaly

• Right upper quadrant pain.

Because not all patients exhibit the full spectrum of the syndrome, a common clinical definition requires the presence of any two of the above-listed features with the onset occurring no later than 14 days from stem cell infusion. Because these clinical manifestations are not specific to VOD, all other causes of hepatic dysfunction must be excluded. Another condition that may mimic hepatic VOD is nodular regenerative hyperplasia of the liver, a diffuse nonfibrotic nodulation of the liver with areas of regenerative activity alternating with areas of atrophy. This syndrome effects the same transplantation population at risk for hepatic VOD, and both conditions are frequently associated with the development of ascites. Although no specific treatments are available for either entity, the mortality rate is considerably higher for patients who develop hepatic VOD than for those who develop nodular regenerative hyperplasia.

Predisposing Factors

The cause of VOD remains unknown; however, patients with the following have an increased risk:

• Preexisting hepatitis (one of the most strongly predictive risk factors)

• Elevated liver function tests

• Refractory leukemia

• Underlying metastatic tumor in the liver

• Positive CMV serologic status

• Conditioning agents (such as TBI, busulfan, cytosine arabinoside)

• Mismatched or unrelated allogeneic transplants

• Certain antimicrobial agents (especially vancomycin and acyclovir when given before transplantation) have also been implicated.

Prophylaxis

Lower or fractionated doses of BCNU (carmustine), lower total doses of TBI or shielding of the liver during TBI, use of T-cell-depleted marrow, use of ursodeoxycholic acid, and continuous infusion of low-dose heparin have been used to reduce toxicity.

Treatment

• Supportive care

• Sodium restriction

• Spironolactone therapy

• Thrombolytic therapy (continuous infusion of heparin during pretrans-plant conditioning and through the first 2 weeks post-transplant in a dose of 100-150 units/kg/day or recombinant human tissue plasminogen activator [t-PA] and heparin or antithrombin [AT] infusion if AT levels are low)*

• Prostaglandin E (may be a promising agent in prophylaxis)

• Portacaval shunting

• Liver transplantation.

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