Initiating Cytoreductive Therapy in Polycythemia Vera

Srdan Verstovsek, MD:Our patient, who is younger than age 60 and has never had a thrombotic episode, is at low risk for thrombosis among the population of patients with polycythemia vera. Our patient was properly started on therapy with low-dose aspirin (81 mg) and phlebotomy with a goal to decrease the hematocrit level to below 45%. Now, a few months later, the patient is back in our office with continuous requirements for phlebotomies and continuous presence of general symptoms. This would be reflective of uncontrolled red blood cell count, or, in other words, uncontrolled polycythemia vera. One needs to remember that we are talking about a person, not just about controlling a number. We control the number to decrease the risk of thrombosis to save the life of the patient but also to improve their quality of life. So, there is a goal to control thrombotic risk. A secondary goal of therapy for polycythemia vera is to control the symptoms.

Despite the phlebotomies, this patient is still symptomatic. In this case, it is very reasonable to say that something else needs to be done. If the phlebotomies are not controlling the symptoms, and the control of the blood cell count does not project into improvement in quality of life, then one needs to think about the introduction of cytoreductive therapy. Cytoreductive therapy is treatment that works to control the blood cell count without allowing the blood cell count to go up and down.

Basically, phlebotomy is introduced when the number is high. Then you lower it. Then it goes up. Then you lower it with phlebotomies. So, it goes up and down and up and down. The symptoms are obviously not very well controlled if you allow a time period when the blood cell count is high. Cytoreductive therapy will level it off and keep the number low all the time. This will likely result in better control of the symptoms. So, in our particular case, although the patient is at low risk for thrombosis, it is reasonable to introduce cytoreductive therapy. I would introduce hydroxyurea as a first-line option.

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