Treatment Approach for Myelofibrosis-Associated Splenomegaly

Risk-Stratified Approach

For intermediate-2 or high-risk disease patients, Ruxolitinib is recommended as first-line therapy for splenomegaly, according to the International Working Group for Myelofibrosis Research and Treatment 1, 2, 3
For intermediate-1 risk disease with highly symptomatic splenomegaly, Ruxolitinib is recommended as first-line therapy, as suggested by the European LeukemiaNet 2, 3
For intermediate-1 risk disease without severe symptoms or low-risk disease, Hydroxyurea is recommended as first-line therapy, based on guidelines from the American Society of Hematology 2, 3
Ruxolitinib is also recommended for patients with splenomegaly not responding or intolerant to hydroxyurea, according to the National Comprehensive Cancer Network 2, 3

Hydroxyurea is the conventional first-line therapy for splenomegaly, particularly in lower-risk disease, with a reduction of spleen volume occurring in approximately 40% of patients, as reported by the European LeukemiaNet 1, 4

For hydroxyurea-refractory disease, alternative myelosuppressive agents such as intravenous cladribine, oral melphalan, and oral busulfan may be considered, as recommended by the American Society of Clinical Oncology 4, 5

Splenectomy remains a viable palliative treatment option for drug-refractory symptomatic splenomegaly, with specific indications including symptomatic portal hypertension, drug-refractory marked splenomegaly, and established RBC transfusion-dependent anemia, as suggested by the Society of Surgical Oncology 4, 6
The perioperative mortality is between 5-10%, with postsplenectomy complications occurring in approximately 50% of patients, according to the American College of Surgeons 5, 7

Involved-field radiotherapy provides symptomatic relief of mechanical discomfort from hepatosplenomegaly, with a response typically lasting 3-6 months, as reported by the American Society for Radiation Oncology 4, 5

Allogeneic stem cell transplantation is the only potentially curative approach for myelofibrosis, recommended for transplant-eligible patients with high or intermediate-2 risk, as well as those with intermediate-1 risk and refractory transfusion-dependent anemia, according to the European Society for Blood and Marrow Transplantation 2, 3, 5, 7

Before splenectomy, cytoreduction and anticoagulants are recommended prophylactic measures, and platelet count should be kept below 400 × 10⁹/L to prevent postoperative extreme thrombocytosis, as suggested by the American College of Surgeons 5, 7