What are the treatment options for splenomegaly?

Treatment Options for Splenomegaly

Ruxolitinib is recommended as first-line treatment for splenomegaly in patients with intermediate-2 or high-risk myelofibrosis, while hydroxyurea is the first-line treatment for low-risk or intermediate-1 risk disease without highly symptomatic splenomegaly. 1

Pharmacological Management Based on Disease Risk

Myelofibrosis-Associated Splenomegaly

• High-risk/Intermediate-2 risk disease:

  • First-line: Ruxolitinib 1
  • Demonstrated superior spleen volume reduction in COMFORT trials with high-quality evidence 1

• Intermediate-1 risk disease:

  • With highly symptomatic splenomegaly (local symptoms, impaired food intake): Ruxolitinib 1
  • Without highly symptomatic features: Hydroxyurea 1

• Low-risk disease:

  • First-line: Hydroxyurea 1
  • Achieves spleen volume reduction in approximately 40% of patients 1

Hydroxyurea-Refractory Disease

For patients not responding to hydroxyurea, options include:

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

Radiotherapy Options

• Low-dose splenic irradiation provides temporary symptomatic relief (3-6 months duration) 1
• Typical dosing: 0.1-0.5 Gy in 5-10 fractions 1
• Caution: Associated with >10% mortality rate from cytopenia complications 1
• Best used as a palliative approach rather than long-term management 1

Surgical Management: Splenectomy

Splenectomy remains a viable option for drug-refractory splenomegaly 1 with specific indications:

Indications:

• Symptomatic portal hypertension (variceal bleeding, ascites) 1
• Drug-refractory painful splenomegaly 1
• Severe cachexia associated with splenomegaly 1
• Established RBC transfusion-dependent anemia 1

Important Considerations:

• Perioperative mortality: 5-10% 1
• Complications occur in approximately 50% of patients 1
• Complications include:
  • Surgical site bleeding
  • Thrombosis
  • Subphrenic abscess
  • Accelerated hepatomegaly
  • Extreme thrombocytosis
  • Leukocytosis with excess blasts 1

Pre-Splenectomy Requirements:

• Good performance status
• No evidence of disseminated intravascular coagulation
• Prophylactic cytoreduction and anticoagulants
• Platelet count maintained below 400×10⁹/L 1
• Experienced surgical team 1

Allogeneic Stem Cell Transplantation

Consider allogeneic stem cell transplantation for:

• All transplant-eligible patients with high or intermediate-2 risk disease 1
• Transplant-eligible patients with intermediate-1 risk who have:
  • Refractory, transfusion-dependent anemia
  • Peripheral blood blasts >2% in repeated measurements
  • Adverse cytogenetics
  • High-risk mutations 1

Monitoring and Follow-up

• Regular blood count monitoring every 6-12 months 2
• Abdominal ultrasound every 6 months for patients with underlying liver disease 2
• Patients should avoid contact sports to decrease risk of splenic rupture 2, 3

Potential Pitfalls

• Performing splenectomy in patients with severe thrombocytopenia (may indicate impending 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

Complications to Monitor

• Acute infections
• Worsening cytopenias
• Splenic infarction or rupture
• Portal vein thrombosis 2

The treatment approach should be guided by disease risk stratification, symptom burden, and patient-specific factors, with the primary goal of reducing morbidity and mortality while improving quality of life.