A 72-year-old woman presents with fatigue, weight loss, and massive splenomegaly. Blood film shows teardrop cells, giant platelets, and circulating CD34+ blasts. Bone marrow trephine shows dry tap. JAK2 V617F mutation is positive. Fibrosis grade MF-2 on WHO grading. IPSS score is intermediate-2. What is the most appropriate disease-modifying therapy?

• A Hydroxyurea alone
• B Imatinib mesylate
• C Thalidomide and prednisolone
• D Ruxolitinib (JAK1/2 inhibitor) ✓

Explanation

Ruxolitinib (a JAK1/2 inhibitor) is the first-line disease-modifying therapy for intermediate-2 or high-risk myelofibrosis (COMFORT-I and COMFORT-II trials), significantly reducing splenomegaly and constitutional symptoms and improving survival. Hydroxyurea reduces spleen size but does not modify the disease course or improve survival. Imatinib is for BCR-ABL positive CML. Thalidomide/prednisolone is used for anaemia in MF but does not address disease modification.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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