What is the treatment for splenomegaly?

Treatment of Splenomegaly

For symptomatic splenomegaly, JAK inhibitors (ruxolitinib) are the first-line treatment for patients with intermediate-2 or high-risk myelofibrosis, while hydroxyurea is recommended as first-line therapy for patients with low or intermediate-1 risk disease. 1

Approach to Splenomegaly Treatment

Treatment for splenomegaly should be directed at the underlying cause, with specific interventions based on disease etiology, symptom severity, and risk stratification:

First-line Medical Therapy

1. Myeloproliferative disorders (most common cause):

   • JAK inhibitors: Ruxolitinib is recommended as first-line therapy for symptomatic splenomegaly in patients with intermediate-2 or high-risk myelofibrosis 1
   • Hydroxyurea: First-line therapy for low or intermediate-1 risk disease with an overall response rate of approximately 40% 1
   • Note: After 1 year of hydroxyurea treatment, about 80% of patients require alternative therapy 1

2. For hydroxyurea-refractory disease, alternative myelosuppressive agents include:

   • Intravenous cladribine (5 mg/m²/day in a 2-hour infusion for 5 consecutive days, repeated for 4-6 monthly cycles)
   • Oral melphalan (2.5 mg three times weekly)
   • Oral busulfan (2-6 mg/day with close monitoring of blood counts) 1

Radiation Therapy

• Low-dose splenic irradiation: Provides temporary symptomatic relief (3-6 months) of mechanical discomfort from hepatosplenomegaly 1

  • Typically given at 0.1-0.5 Gy in 5-10 fractions
  • Associated with >10% mortality rate from consequences of cytopenia
  • Not recommended for routine use due to transient benefit and risk of severe cytopenias 1

• Low-dose radiation therapy: Treatment of choice for symptomatic extramedullary hematopoiesis in sites other than the spleen and liver 1

Surgical Management

• Splenectomy: Viable option for drug-refractory symptomatic splenomegaly 1

  • Indications:

    • Symptomatic portal hypertension (variceal bleeding, ascites)
    • Drug-refractory painful splenomegaly
    • Severe cachexia associated with splenomegaly
    • Transfusion-dependent anemia refractory to drug therapy 1, 2

  • Risks:

    • Perioperative mortality: 5-10%
    • Complications in approximately 50% of patients
    • Complications include surgical site bleeding, thrombosis, subphrenic abscess, accelerated hepatomegaly, extreme thrombocytosis, and leukocytosis 1

  • Contraindications:

    • Poor performance status
    • Clinical or laboratory evidence of disseminated intravascular coagulation
    • Severe thrombocytopenia (marker of impending leukemic transformation) 1, 2

Special Considerations

1. Pre-transplant splenomegaly: Patients with myelofibrosis and splenomegaly ≥5 cm (particularly >15 cm below left costal margin) could benefit from treatment to reduce spleen size before allogeneic hematopoietic cell transplantation 3

2. Associated anemia: May require specific treatment with:

   • Erythropoiesis-stimulating agents
   • Androgens (danazol 400-600 mg daily)
   • Immunomodulators (thalidomide, lenalidomide)
   • Corticosteroids 1

3. Splenic infarction: Cytoreductive therapy can lead to successful regression without surgical intervention. Splenectomy should be limited to patients with persistent symptoms and complications such as hemorrhage or emergency conditions 1

4. Prevention of complications:

   • Patients should avoid contact sports to decrease risk of splenic rupture 2, 4
   • Monitor for signs of acute infection, worsening cytopenias, and portal vein thrombosis 2

Monitoring Response

• Regular assessment of spleen size (physical examination and/or imaging)
• Complete blood count to monitor for improvement in cytopenias
• Assessment of constitutional symptoms
• Consider alternative therapy if no response after appropriate trial period

Pitfalls to Avoid

• Performing splenectomy in patients with severe thrombocytopenia (may indicate leukemic transformation) 2
• Underestimating risks of splenectomy in patients with portal hypertension 2
• Overlooking splenic sequestration as a life-threatening complication in sickle cell disease 2
• Failing to recognize malignant infiltration in patients with massive splenomegaly 2

Treatment of splenomegaly requires careful consideration of the underlying cause, risk stratification, and patient-specific factors to optimize outcomes and minimize complications.