Switching Therapy in Polycythemia Vera

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Srdan Verstovsek, MD:The change in therapy is particularly tricky. What is the cutoff for the white blood cell count to be significant? One would say above normal, which would be above 11. More reasonably, we say progressive leukocytosis, which means a steady increase in white blood cell count over time. We don’t really know which number or which cutoff to use to say that it’s significant or not. In my own practice, I’m sensitive to progressive leukocytosis as a factor that will lead me to introduce cytoreductive therapy, even in a low-risk patient who otherwise has good control of the red blood cell count with phlebotomy.

Progressive leukocytosis, or a steady increase in white blood cell count, is a factor that we use to judge whether there is a need for dose adjustment of cytoreductive therapy or an introduction of cytoreductive therapy, even in the low-risk patient who has a phlebotomy in place with good control of the red blood cell count. You can imagine a case in which phlebotomy does the job of controlling the red blood cell count, but there is a steady increase in white blood cell count from 11 to 15, to 18, to 20. That bothers me as a physician. I would introduce cytoreductive therapy to control the white cell count.

The same can be said for a patient who is already on hydroxyurea. If the hydroxyurea is controlling some of the parameters that we look for—red blood cells or platelets or the spleen—but there is steady progressive leukocytosis, where the white cell count is steadily increasing despite the dose adjustments, that is something that is clinically relevant for me. I would consider a change to second-line therapy.

Transcript edited for clarity.


June 2016

  • A 49-year old male presents with headache, fatigue, and pain under his left ribs
  • PMH includes depression and newly diagnosed hypertension
  • Physical exam: BP, 160/90; abdominal exam reveals splenomegaly — spleen palpable 6 cm below costal margin
  • Laboratory values:
    • Hb=20.7 g/L
    • HCT= 59.4%
    • WBC=10.2x109/L
    • Platelets= 325 x109/L
  • Bone marrow biopsy:
    • MF-1 fibrosis and megakaryocytic hyperplasia with atypia
    • JAK2-positive
  • Patient was started on phlebotomy as needed and aspirin 81 mg

October 2016

  • Patient returns 4 months later with continued headache and dizziness
  • He has had 3 phlebotomies in the past 3 months
  • Patient was started on hydroxyurea 1000 mg/day

January 2017

  • Patient returns 3 months later with abdominal fullness, continued fatigue, difficulty concentrating, fever, and leg ulcer
  • Laboratory values:
    • Hb= 22.4 g/L
    • HCT= 65.3%
    • WBC=13.3x109/L
    • Platelets=153x109/L
  • Patient is started on ruxolitinib
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