What is the treatment for post-transplant Veno-Occlusive Disease (VOD)?

Treatment of Post-Transplant Veno-Occlusive Disease (VOD)

Defibrotide is the only FDA-approved treatment for post-transplant VOD with renal or pulmonary dysfunction and should be initiated immediately upon diagnosis at a dose of 6.25 mg/kg IV every 6 hours for a minimum of 21 days or until resolution of symptoms. 1

First-Line Treatment

Defibrotide Therapy

• Dosing: 6.25 mg/kg IV every 6 hours administered as a 2-hour infusion 1
• Duration: Minimum of 21 days; continue until resolution of VOD signs and symptoms 1, 2
  • Studies show 60% of patients require treatment beyond 21 days 2
  • 15% of patients may need treatment beyond 28 days 2
• Efficacy: Complete resolution of VOD occurs in approximately 75% of patients 3
• Survival benefit: Day 100 survival rate is significantly higher in patients who achieve complete response (92.5% vs 37.3%) 2

Supportive Care Measures

• Fluid management: Judicious fluid balance management is critical 4
• Diuretics: High-dose diuretics to manage fluid overload 5
• Oxygen therapy: Supplemental oxygen to maintain SpO2 >92% 5
• Positioning: Upright positioning to reduce venous return and improve ventilation 5

Monitoring During Treatment

• Continuous monitoring for bleeding complications (most common adverse events) 1
• Regular assessment of:
  • Liver function tests
  • Renal function
  • Respiratory status
  • Fluid balance
• Early recognition of treatment response or progression

Management of Complications

Hemorrhagic Complications

• Most common adverse events with defibrotide include 3:
  • Hematuria (43%)
  • Epistaxis (18%)
  • Hypotension (11%)
• Severe hemorrhage occurs in approximately 7% of patients 3
• Management: Withhold or discontinue defibrotide if significant bleeding occurs 1

Hypersensitivity Reactions

• Discontinue defibrotide if severe or life-threatening allergic reactions occur 1
• Treat according to standard of care and monitor until resolution 1

Prophylaxis Considerations

For high-risk patients undergoing transplant, prophylactic measures should be considered:

• Ursodeoxycholic acid is recommended for VOD prophylaxis 6, 4
• Defibrotide prophylaxis (6.25 mg/kg IV four times daily) should be considered in high-risk patients 4:
  • Pre-existing hepatic disease
  • Second myeloablative transplant
  • Allogeneic transplant for leukemia beyond second relapse
  • Busulfan-containing conditioning regimens
  • Prior treatment with gemtuzumab ozogamicin

Special Considerations

• Early initiation is crucial: Prompt initiation of defibrotide on day of diagnosis is associated with better outcomes (71% of successful cases started on day of diagnosis) 3
• Minimize interruptions: Continuous therapy without dosing interruptions may be key to successful treatment 3
• Contraindications: Defibrotide should not be used with concomitant systemic anticoagulant or fibrinolytic therapy 1
• Early consultation: Early discussion with critical care specialists and hepatology is recommended 4
• Transplant evaluation: Referral for liver transplantation should be considered in severe cases not responding to defibrotide 6

Pitfalls to Avoid

• Delaying diagnosis and treatment initiation
• Premature discontinuation of defibrotide before complete resolution
• Failure to provide adequate supportive care
• Inappropriate use of anticoagulants or fibrinolytics during defibrotide treatment
• Inadequate monitoring for hemorrhagic complications

Early diagnosis, prompt initiation of defibrotide, and comprehensive supportive care are essential for improving outcomes in patients with post-transplant VOD.