A 62-year-old man with polycythemia vera (PV) is on hydroxyurea. Despite hydroxyurea at 2g/day, haematocrit remains > 45%, platelet count is 900,000/µL, and he develops new splenomegaly. He has JAK2 V617F mutation. Per ELN 2018 criteria, what defines 'resistance/intolerance' to hydroxyurea in PV?
- A Any toxicity at any dose of hydroxyurea requiring dose reduction
- B Failure to maintain haematocrit < 45% without phlebotomy, OR platelet count > 400,000/µL, OR WBC > 10,000/µL, at the maximum tolerated dose ✓
- C Progression to myelofibrosis within 2 years of starting therapy
- D JAK2 allele burden > 50% after 12 months of therapy
Explanation
The ELN 2018 criteria for hydroxyurea resistance in PV require at least ONE of the following: need for phlebotomy to keep haematocrit < 45% after 3 months at hydroxyurea 2 g/day; uncontrolled myeloproliferation (platelets > 400,000 or WBC > 10,000/µL) after 3 months at 2 g/day; failure to reduce massive spleen by > 50% on palpation after 3 months at 2 g/day; or absolute neutrophil count < 1,000/µL or platelets < 100,000/µL or Hb < 10 g/dL at the lowest dose achieving a complete or partial response (intolerance). Leg ulcers, fever, or mucocutaneous toxicity also define intolerance. These criteria justify switching to ruxolitinib (JAK1/2 inhibitor) per current guidelines.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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