Aaron Gerds, MD, MS: Hi. Welcome to this discussion of the updated NCCN [National Comprehensive Cancer Network] guidelines for polycythemia vera [PV]. It’s a pleasure to be with you today. My name is Aaron Gerds. I’m [an] associate professor of medicine at the Cleveland Clinic Taussig Cancer Institute [in Ohio]. I also serve as the medical director for the Case Comprehensive Cancer Center Clinical Research Office, as well as the deputy director for clinical research here at the Taussig Cancer Institute. With that, we will jump into our questions.

For most people there aren’t broadly established risk factors for developing polycythemia vera. And again, I’m specifically speaking about polycythemia vera, the disease driven by JAK/STAT activation within the bone marrow as opposed to a secondary erythrocyte ptosis where the body is asking for more red cells via erythropoietin and the red cells are being produced as a response. [With] polycythemia vera we know that there are some associations with prior chemotherapy or radiation for other cancers. There are certainly family and familial predisposition syndromes as well as emerging data linking MPNs [myeloproliferative neoplasms] in general with Agent Orange exposure. But outside that, there are few things that we know that can directly increase one’s risk for developing polycythemia vera. For most people, it’s acquired and simply acquired during the lifespan of someone. We know that JAK mutations are common in this thing called clonal hematopoiesis of indeterminate potential [CHIP]. And those can ultimately turn into cases of polycythemia vera.

When we think about complications associated with PV in 2 different categories, one is certainly disease progression, where polycythemia vera over time becomes a more aggressive form, [such as] post–polycythemia vera, a myelofibrosis, or even accelerated or blast phase MPN, which is akin to acute myeloid leukemia. The other way we think about complications of PV are the more immediate effects, whether we’re talking symptoms related to cytokine release [syndrome] like night sweats and fevers, or due to increased spleen size, like early satiety and abdominal discomfort, as well as the overall arching risk of bleeding and clotting. So when we think about treatment of [PV], we tend to think about the latter most often—controlling symptoms that may be associated with polycythemia vera and minimizing thrombosis or blood clot risk.

Most often when we talk about low- and high-risk polycythemia vera, we’re talking about thrombosis risk or the risk of developing a blood clot, either arterial or venous, and age is a strong predictor of blood clot. As we age, our risk for blood clots go up, as well as a prior history of blood clots. Nothing predicts the future like the past. All the patients or almost all patients, I would probably say, have a JAK2 V617F mutation, which is associated with a higher risk of thrombosis as well. There are other things that are nodded toward but are not part of the established criteria for determining high or low risk, like elevated white blood cell count, among others. That can be an additional risk factor for having a blood clot. So traditionally we think about age and thrombosis history, but we also look to other things like high white blood cell count as other predictors for blood clots in patients with polycythemia vera.

So while is not clearly defined in low-risk PV, certainly these folks can land in the hospital, and they can lie in a hospital for all kinds of reasons. They can be hospitalized for other medical conditions that they may have. Often, if we think about PV-related admissions, thrombosis is going to be the big one, whether we’re talking about pulmonary emboli or, even more seriously, blood clots in the liver and the other vessels supplying the gut. Those are certainly acute and life-threatening clots as well. Patients with polycythemia vera can also be admitted with strokes and heart attacks, and all of these things can be addressed most directly based on the regionality of the blood clot, but also within the context of the setting of the polycythemia vera controlling the other blood counts, as well as potentially lifelong anticoagulation.

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