Diagnosis and Evaluation in Polycythemia Vera

Evaluating treatment, diagnostic criteria, and risk-assessment tools in polycythemia vera.

Ruben A. Mesa, MD: The diagnostic criteria for polycythemia vera that we follow are based on the World Health Organization [WHO] 2016 Guidelines, and fundamentally they begin with the presumption that you are suspicious if you have P [polycythemia] vera. Why might you be suspicious if someone has P vera? Clearly unexplained erythrocytosis, an unexplained vascular event, sometimes unexplained leukocytosis, thrombocytosis, or others, particularly if they might have erythrocytosis that is masked because they’ve had iron deficiency or for some other reason.

Fundamentally, it starts with a clinical suspicion with secondary things you’re trying to exclude in your differential diagnosis: smoking or other chronic hypoxic states, sleep apnea, use of androgens is a common cause of secondary erythrocytosis, EPO [erythropoietin]–producing tumor. The diagnosis fundamentally is around unexplained erythrocytosis and the presence of a mutation explaining that. Namely, the JAK2 V617F or the exon 12 mutation.

The WHO criteria, once you prove erythrocytosis, want you to establish a diagnostic molecular marker such as the JAK2, and look at the bone marrow for the typical histological features as it relates to erythroid precursors, hypercellularity, and others consistent with P vera.

Additionally, there are minor criteria that can be considered, such as a suboptimal EPO level, if an individual lacks either of the 2 JAK2 mutations. There are individuals who have JAK2-negative P vera, but this is not common in a diagnosis of an exclusion and typically need a solid case that bone marrow, low EPO, and others help establish.

Assessing risk for a patient with polycythemia vera is multifaceted. I like to think of both assessing the disease burden and the risk. The disease burden for a patient with P vera includes risk of thrombosis, risk of bleeding, potential P vera–related symptoms such as pruritis, night sweats, and difficulties concentrating, and a variety of catabolic symptoms. Additionally, sometimes they can have splenomegaly. All of that is part of burden.

Risk is 2-fold. One, there are historical criteria for risk of thrombotic or vascular events, including age over 60 or having a prior unexplained thrombotic or vascular event. Over time we have developed additional prognostic factors, which can include leukocytosis, age, prior events, and other higher-risk molecular features, such as ASXL1 or others. I find that the disease burden concept is the most relevant in terms of trying to make an impact for the patients. The prognosis piece is helpful, but prognosis is probably the most relevant concept for individuals with myelofibrosis that have typically a more aggressive disease.

Srdan Verstovsek, MD, PhD: Polycythemia vera is the disease of the bone marrow that makes too many red blood cells. In many patients, white blood cells and platelets as well. But red blood cells are present in all, and there is a good correlation between having a blood clot and too many red blood cells.Therefore, to decrease the thrombotic risk that is paramount in assessing patients with polycythemia vera, we would like to control the red blood cell count. We talk about hematocrit as a goal of therapy, to control hematocrit.

Hematocrit is the percentage of blood that is made up of the red blood cells, so it comes as a percentage. We want to have strict control of hematocrit in terms of having it below 45%. That’s the No. 1 goal in patients with polycythemia vera. We want to that in patients who are at a high risk for thrombosis, and maybe two-thirds of the polycythemia vera patients are such. These are defined by age over 60 or history of a blood clot. These are the 2 factors we use, history of blood clot or older than 60. These are patients at a high risk for blood clot.

In these patients, in addition to worrying about the hematocrit, we worry about the white blood cells and platelets. In these patients, we would like to control all 3 lines. If the spleen is enlarged, as it may be in some patients, and if they have a bad quality of life, we want to control them as well.

The usual goal of therapy is, No. 1, control the hematocrit, and we check the blood count maybe weekly at the beginning, phlebotomize if necessary, and then as phlebotomy kicks in and eliminates the red blood cells a lot and people become iron deficient, maybe you don’t need to follow the patients too often anymore—maybe every 2 weeks, then every month, then every 3 months. That would be a good standard practice after a while when phlebotomy is eliminated. But with the cytoreduction therapy, there would be medications that are given to high-risk patients.

Cytoreductive therapy would be controlling hematocrit, white cells, and platelets. In that case, we’re talking about complete hematologic response. The follow-up is similar in a low- or high-risk patient. The goals are well defined and built in to our NCCN [National Comprehensive Cancer Network] Guidelines.

Transcript Edited for Clarity

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