A 65-year-old man presents with splenomegaly, constitutional symptoms, and JAK2 V617F mutation positive. Peripheral blood shows leukoerythroblastic picture; bone marrow biopsy shows grade 2 fibrosis. DIPSS-Plus score categorizes him as intermediate-2 risk. Which is the most appropriate disease-modifying therapy?
- A Hydroxyurea to control splenomegaly
- B Interferon-alfa-2a to reduce JAK2 allele burden
- C Ruxolitinib (JAK1/2 inhibitor) ✓
- D Anagrelide to reduce platelet count and splenomegaly
Correct answer: C. Ruxolitinib (JAK1/2 inhibitor)
Explanation
Ruxolitinib is the first-line disease-modifying therapy for intermediate-2 and high-risk primary myelofibrosis as established by COMFORT-I and COMFORT-II trials, which demonstrated significant reduction in splenomegaly and constitutional symptoms, and improved overall survival. Hydroxyurea provides symptom control but does not modify disease or improve survival. Interferon-alfa reduces JAK2 allele burden but is used for low-risk early disease or in young patients, not intermediate-2/high-risk. Anagrelide lowers platelets but has no evidence in myelofibrosis.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.