Ruben Mesa, MD: For the patient presenting with polycythemia vera, as we approach the diagnosis, clearly, we start with really what was our reason for suspicion for their having polycythemia vera to begin with. Did they have a thrombotic event? Did they have an unexpected increase in the counts, unexpected splenomegaly, or unexpected symptoms ranging from headache, or fatigue, to difficult pruritus? Our diagnosis really begins with our preclinical suspicion because that heavily informs our work-up.
First, we clearly begin with the blood counts, and the unexplained erythrocytosis is clearly a key cornerstone. By our 2016 WHO criteria, that’s the starting place. The red blood cell count is up; it’s unexplained. Clearly, if there is leukocytosis and thrombocytosis at the same time, I’m even that much more suspicious. Second, we look at the presence of the JAK2 V617F mutation or the JAK2 exon 12. They typically are tied together these days with reflex testing. The presence of that mutation and unexplained erythrocytosis really take you most of the way there to a diagnosis.
A bone marrow aspirate and biopsy are included in the 2016 criteria, as well, as if the JAK2 mutation is not present, a subnormal erythropoietin level. Now, in there, as we identify the risk, we diagnose the patient. We then assess risk on the basis of age and the basis of prior thrombotic events. Those clearly increase risk. Higher leukocyte count clearly increases the rate of thrombotic event and likely increases the rate of progression.
Now, as we think about goals of therapy, they include trying to 1) control the hematocrit and 2) by European LeukemiaNet criteria, control leukocytosis and thrombocytosis if present, control splenomegaly if it’s present, and control symptoms if they are present—fatigue headaches, spleen-related symptoms, pruritus. So, the way I frame it for patients, what is the burden of their disease, specifically in terms of risk and disease burden? Then we develop our goals of therapy accordingly.
Transcript Edited for Clarity