What is the evaluation and management plan for a patient with splenomegaly (enlarged spleen)?

Evaluation and Management of Splenomegaly

The evaluation of splenomegaly requires a systematic diagnostic approach followed by targeted management of the underlying cause, with JAK inhibitors being the first-line treatment for symptomatic splenomegaly in myeloproliferative disorders, while hydroxyurea remains an alternative option for patients who cannot receive JAK inhibitors. 1, 2

Diagnostic Assessment

• Splenomegaly is defined as spleen length greater than 13 cm when measured in the coronal plane on imaging studies 2
• Initial evaluation should include:
  • Complete blood count with differential and reticulocyte count 2
  • Abdominal imaging (CT or ultrasound) to confirm splenomegaly and evaluate for associated findings 2
  • Assessment for signs of systemic illness that commonly cause splenomegaly, including:
    • Hematologic malignancies (lymphoma, leukemia, myeloproliferative disorders) 2
    • Liver disease with portal hypertension 2
    • Infections (mononucleosis, malaria, bacterial endocarditis) 3

Common Etiologies

• Myeloproliferative neoplasms (primary myelofibrosis, polycythemia vera, essential thrombocythemia) 1
• Lymphoproliferative disorders (lymphomas, leukemias) 2
• Portal hypertension secondary to liver disease 3
• Infections (viral, bacterial, parasitic) 3
• Inflammatory conditions (sarcoidosis, systemic lupus erythematosus) 3
• Storage diseases (Gaucher disease) 3

Management Approach

Treatment of Underlying Cause

• The primary goal is to identify and treat the underlying condition causing splenomegaly 2
• For myeloproliferative disorders:
  • JAK inhibitors (ruxolitinib) are first-line therapy for symptomatic splenomegaly, with dramatic effects on spleen reduction and symptom control 1
  • Hydroxyurea is an alternative for controlling symptomatic splenomegaly with approximately 40% response rate 1
  • For patients with massively enlarged spleen (>20 cm below costal margin), consider splenectomy, splenic irradiation, or JAK inhibitors 1

Specific Management for Myelofibrosis-Associated Splenomegaly

• JAK inhibitors:

  • Ruxolitinib is the first-in-class drug approved for myelofibrosis treatment 1
  • Phase III studies demonstrated ≥35% reduction in spleen volume at 24-48 weeks of treatment 1
  • Caution: Thrombocytopenia and worsening anemia are common adverse events 1
  • Avoid abrupt interruption of ruxolitinib as it can provoke a shock-like syndrome 1

• Hydroxyurea:

  • Previously first-line therapy before JAK inhibitors 1
  • Achieves spleen volume reduction in approximately 40% of patients 1
  • After 1 year of treatment, about 80% of patients require alternative therapy 1

• Splenectomy:

  • Consider for drug-refractory symptomatic splenomegaly 1
  • Indications include symptomatic portal hypertension, painful splenomegaly associated with cachexia, and transfusion-dependent anemia 1
  • Perioperative mortality is 5-10% with morbidity up to 25% 1
  • Requires experienced surgical team and critical care support 1

• Splenic irradiation:

  • Option for patients who don't tolerate JAK inhibitors and are poor surgical candidates 1
  • Typically given at a dose of 0.1-0.5 Gy in 5-10 fractions 1
  • Benefits are transient (3-6 months) with risk of severe cytopenias 1
  • Not recommended for routine use 1

Management of Associated Complications

• For anemia (hemoglobin <10 g/dL):

  • Erythropoiesis-stimulating agents (response in 23-60% of patients) 1
  • Androgens or danazol (response in 30-40% of patients) 1
  • Low-dose thalidomide with prednisone (response in 23-29%) 1
  • Lenalidomide (preferred for patients with del(5q)) 1

• For constitutional symptoms:

  • Often respond to treatment directed at splenomegaly 1
  • JAK inhibitors are particularly effective for symptom control 1

• For non-hepatosplenic extramedullary hematopoiesis:

  • Low-dose radiation therapy (0.1-1 Gy in 5-10 fractions) is the treatment of choice 1

Special Considerations

• Patients with splenomegaly should refrain from contact sports to decrease risk of splenic rupture 3

• For patients undergoing allogeneic hematopoietic cell transplantation:

  • Splenomegaly ≥5 cm below costal margin, particularly when exceeding 15 cm, may benefit from treatment to reduce spleen size before transplant 4
  • Splenomegaly is associated with higher risk of delayed engraftment, graft failure, and worse overall survival after transplantation 4

• For massive splenomegaly (>20 cm in largest dimension or >1000g):

  • Increased risk of complications including pressure on adjacent organs 5
  • Splenectomy may be necessary for both diagnosis and treatment 5

Follow-up

• Regular monitoring of spleen size during treatment of the underlying condition 2
• For patients with lymphoma, response assessment should include measurement of spleen size 2
• Regular follow-up imaging to assess changes in spleen size in response to treatment 2