Myeloproliferative Neoplasms: Chronic Myeloid Leukemia, Essential Thrombocythemia, and Primary Myelofibrosis

Question · easy

A 62-year-old man presents with 2 months of fatigue, early satiety, and a 4-kg weight loss. He takes no medications. Temperature is 37.1 C, and the spleen edge is palpable 8 cm below the left costal margin. Leukocyte count is 87,000/uL with the full spectrum of myeloid maturation on smear, 4% blasts, 6% basophils, and a mild normocytic anemia. Which of the following is the most appropriate next diagnostic test?

Serum erythropoietin level Bone marrow biopsy with reticulin staining Peripheral blood testing for BCR-ABL1 by cytogenetics, FISH, or PCR JAK2 V617F mutation testing

Question · medium

A 68-year-old woman is found to have a platelet count of 940,000/uL on routine testing. She has no history of thrombosis or bleeding. Testing reveals a JAK2 V617F mutation; iron studies are normal. According to risk-adapted management of essential thrombocythemia, what is the most appropriate initial therapy?

Observation only Low-dose aspirin plus cytoreductive therapy with hydroxyurea Plateletpheresis Lifelong anticoagulation with warfarin

Question · hard

A 47-year-old man with chronic-phase CML initially achieved a complete cytogenetic response on imatinib, but 3 years later his BCR-ABL1 transcript levels have risen on serial PCR testing despite confirmed adherence. ABL1 kinase-domain mutation testing identifies a T315I 'gatekeeper' mutation. Which of the following is the most appropriate next step?

Switch to ponatinib (or asciminib), with consideration of allogeneic transplantation Switch to nilotinib Switch to dasatinib Increase the imatinib dose

Question · medium

A 72-year-old man reports progressive fatigue, night sweats, and early satiety. He has massive splenomegaly, hemoglobin 8.9 g/dL, a leukoerythroblastic smear with teardrop red cells, and a 'dry tap' on marrow aspiration. Testing confirms JAK2 V617F-positive primary myelofibrosis with symptomatic splenomegaly. Which of the following statements about JAK inhibitor therapy is correct?

Ruxolitinib or fedratinib improves constitutional symptoms and reduces spleen volume regardless of JAK2 mutational status Splenectomy is preferred over medical therapy for massive splenomegaly JAK inhibitors should be avoided because they worsen constitutional symptoms Ruxolitinib is effective only in patients with homozygous JAK2 V617F mutations

Question · hard

A 66-year-old man with intermediate-risk primary myelofibrosis has become transfusion dependent (hemoglobin 7.6 g/dL) and has persistent constitutional symptoms despite prior ruxolitinib therapy. Which of the following agents is specifically indicated for myelofibrosis patients with anemia and demonstrated superiority over danazol for symptoms, spleen response, and transfusion independence in the MOMENTUM trial?

Momelotinib Fedratinib Anagrelide Ponatinib