What is the treatment approach for splenomegaly?

Treatment Approach for Splenomegaly

For patients with splenomegaly, treatment should target the underlying cause, with specific pharmacological approaches determined by disease risk stratification and symptom severity.

Underlying Cause Assessment

• Splenomegaly is almost always a sign of a systemic condition, with the most common causes in the United States being liver disease, malignancy, and infection 1
• Basic laboratory analysis and abdominal ultrasonography are recommended as first-line steps in determining etiology 1
• Management primarily involves treating the underlying disease process rather than the splenomegaly itself 1

Treatment of Myelofibrosis-Associated Splenomegaly

Risk-Stratified Approach

• For intermediate-2 or high-risk disease patients: Ruxolitinib is recommended as first-line therapy for splenomegaly 2
• For intermediate-1 risk disease with highly symptomatic splenomegaly (local symptoms or impaired food intake): Ruxolitinib is recommended as first-line therapy 2
• For intermediate-1 risk disease without severe symptoms or low-risk disease: Hydroxyurea is recommended as first-line therapy 2
• Ruxolitinib is also recommended for patients with splenomegaly not responding or intolerant to hydroxyurea 2

Hydroxyurea Therapy

• Hydroxyurea is the conventional first-line therapy for splenomegaly, particularly in lower-risk disease 2
• Reduction of spleen volume with hydroxyurea occurs in approximately 40% of patients 2, 3
• The effect of hydroxyurea is often short-lived, requiring consideration of alternative approaches 3

Alternative Cytoreductive Agents

• For hydroxyurea-refractory disease, alternative myelosuppressive agents may be considered, including:
  • Intravenous cladribine (5 mg/m²/day in 2-hour infusion for 5 consecutive days, repeated for 4-6 monthly cycles) 2
  • Oral melphalan (2.5 mg three times weekly) 2
  • Oral busulfan (2-6 mg/day with close monitoring of blood counts) 2

Splenectomy

• Splenectomy remains a viable palliative treatment option for drug-refractory symptomatic splenomegaly 2
• The perioperative mortality is between 5-10%, with postsplenectomy complications occurring in approximately 50% of patients 2
• Specific indications for splenectomy include:
  • Symptomatic portal hypertension (e.g., variceal bleeding, ascites) 2
  • Drug-refractory marked splenomegaly that is painful or associated with severe cachexia 2
  • Established RBC transfusion-dependent anemia 2
• Consideration for splenectomy requires good performance status and absence of clinical or laboratory evidence of disseminated intravascular coagulation 2

Radiation Therapy

• Involved-field radiotherapy provides symptomatic relief of mechanical discomfort from hepatosplenomegaly 2
• The response is typically transient (median duration 3-6 months) 2
• When used, splenic irradiation is given in a total dose of 0.1-0.5 Gy in 5-10 fractions 2
• This approach is associated with >10% mortality rate from consequences of cytopenia 2
• Low-dose radiation therapy is the treatment of choice for non-hepatosplenic extramedullary hematopoiesis 2

Allogeneic Stem Cell Transplantation

• Allogeneic stem cell transplantation (allo-SCT) is the only potentially curative approach for myelofibrosis 2
• Recommended for transplant-eligible patients with IPSS/DIPSS/DIPSS-plus high or intermediate-2 risk 2
• Also recommended for transplant-eligible patients with intermediate-1 risk who present with refractory transfusion-dependent anemia, peripheral blood blasts >2%, adverse cytogenetics, or high-risk mutations 2
• For patients with significant splenomegaly (≥5 cm, especially >15 cm below left costal margin) who are candidates for allo-SCT, treatment to reduce spleen size before transplantation may be beneficial 4

Important Considerations and Precautions

• Patients with limited splenic function require increased vaccination and prophylactic antibiotics for procedures involving the respiratory tract 1
• Patients with splenomegaly should refrain from contact sports to decrease risk of splenic rupture 1
• Before splenectomy, cytoreduction and anticoagulants are recommended prophylactic measures 2
• Platelet count should be kept below 400 × 10⁹/L because of potential for postoperative extreme thrombocytosis 2
• An experienced surgical team is recommended for splenectomy procedures 2