Risk Stratification and the Management of Patients With PV

Ruben A. Mesa, MD, FACP:Risk stratification for polycythemia vera [PV], unlike myelofibrosis, is primarily around the risk of thrombosis, or bleeding, and is less tied to the issue of survival. That may evolve over time, but primarily we are evolving in that part. As we come up with treatment for patients with polycythemia vera, we are, ideally, 1, trying to decrease that risk of blood clots or bleeding; but 2, decrease the burden that that patient faces. Now if you look at the burden that PV patients face, it includes the burden of risk of thrombosis, which we want to diminish; the potential burden of symptomatic difficulties; the potential burden of splenomegaly if it is present; and finally the potential burden of the risk of progression. Something that is very much on patients’ minds as they seek to avoid progression with the disease.

Progression with polycythemia vera has many potential features associated with it. One, there are signs of inadequate therapy. That may be inadequate control of the counts, inadequate control of the symptoms, a thrombotic event, a hemorrhagic event—all of those really are a sign of failure of your goal of therapy. Signs of progression to a different state might include features of moving toward myelofibrosis. That might be further enlargement of the spleen. That might be a change in the symptoms such as inadvertent weight loss or bone pain or fevers. It might be the development of anemia or cytopenias.

And then finally, there can be evidence of moving toward acute leukemia. That tends to be an increase in blasts and further cytopenias. That said, the majority of patients with PV will likely progress to myelofibrosis before they progress to acute leukemia. In this era, it would be very atypical for patients to progress from PV directly into acute leukemia if they had been seen in the past when we used leukemogenic therapy. Back in the era of radioactive phosphorous, there were patients who would have a therapy-associated acute leukemia type of phenotype develop, but fortunately, that is now rare.

Transcript edited for clarity.

Case: 75-Year-Old Man Diagnosed With Polycythemia Vera

January 2018

• A 75-year old man presents to PCP for routine evaluation; feels well but complains of pruritus exacerbated by hot showers
• PE: Unremarkable
• PMH: No prior history of thrombosis, hypertension managed with statin
• Lab values:
  • HGB: 18.9 g/dL
  • Hct: .56 L/L
  • RBC: 68 x 10¹²/L
  • WBC: 10.6 x 10⁹/L
  • Serum EPO: 4.1 mU/mL
• Bone Marrow biopsy declined
• Cytogenetics: JAK-V617Fmutation