Managing Uncontrolled Polycythemia Vera - Episode 4

Using Hydroxyurea in a Patient With Polycythemia Vera

June 20, 2018

Srdan Verstovsek, MD:Although we have 2 factors that we use to separate patients in terms of risk for thrombosis (age over 60 and history of thrombosis), there is a possibility that there is a need for introduction of cytoreductive therapy. Let’s talk about hydroxyurea as a frontline, first-choice option. Occasionally, there is reason to introduce hydroxyurea as treatment in low-risk patients—younger patients, like the one in our case. This would be used for uncontrolled symptoms. You may have control of the blood cell count, but you may not have good control of the symptoms. You need to do something about it. Or you need to frequently do a phlebotomy. Maybe the patient is tired of having phlebotomies or is tired of the side effects of treatment. It is also good to mention progressive leukocytosis, meaning an increase in white cell count, or symptomatic thrombocytosis, increasing platelets, or progressive splenomegaly. These are rare but good-to-remember reasons to introduce hydroxyurea as frontline therapy, even in patients who are at low risk for thrombosis— younger than age 60 and no history of a thrombotic episode. In our case, the patient has uncontrolled symptoms, so it is reasonable to introduce hydroxyurea.

In the United States, by and large, hydroxyurea is the first choice when we talk about introducing cytoreductive therapy in polycythemia vera. Typically, this is given as a 1-pill-a-day regimen (500 mg). There is really no ability to give a 400-mg or 350-mg dose. It’s a 500-mg pill, so most doctors will start with 1 pill a day. Then you can increase the number of pills per day—not every day, but the patient may need 2 pills on weekends. You find your way of managing a patient with a 500-mg pill, either by adjusting the number per day or by cutting back. Some people need 1 pill every other day, not every day. So, 1 pill a day would be the usual starting point.

In patients who have really fast-growing cells, meaning that phlebotomy requirement is very high, or in cases where progressive leukocytosis happens, where the white cell count starts to grow, you may even introduce 2 pills a day (1000 mg). It is very reasonable to try 1 or 2 pills, but the point is that not everybody is the same. You need to follow that patient and, in 3 or 4 weeks, reassess to see whether the dose that was prescribed is perhaps too strong or not good enough. You may need to adjust the dose.

The first 3 or 4 months is a time period where one should see the patient who started on hydroxyurea more often—maybe every 3 or 4 weeks—to be able to adjust properly and achieve the goal. The goal is to normalize the blood cell count and eliminate the symptoms.

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