Ruben Mesa, MD: One of the evolutions in our understanding of polycythemia vera is that it is about more than just the red blood cells. These are myeloid stem cell disorders of which the implications are across the red blood cells, the white blood cells, and the platelets. A higher white blood cell count for me probably is a red flag on 2 levels: a higher rate of thrombotic events or a higher rate of progression. Now, why more thrombotic events? I suspect that it is the biology. The interaction of the red blood cells, the white blood cells, and the platelets, as it has to do with the microcirculation, probably is at play in terms of how those thrombotic events actually form. It has implications in terms of controlling the disease more than just controlling the hematocrit. So, the white blood cell count is an important factor.
The addition in the NCCN guidelines, including now myeloproliferative neoplasms, is important. When we recognize these are clonal neoplasms, the management of these patients in a standardized way across the United States through guidelines, I think, is a big advance. Now, specific things that those guidelines help to address are recognizing the risk associated with the disease but also the importance of really controlling the disease, the early initiation of cytoreductive therapy, and recognizing what those goals are. So, those guidelines call for us to 1) adequately control the hematocrit, to be sure it’s under 45, and 2) over time see the patient require fewer phlebotomies or become largely phlebotomy independent. Next, adequately controlling the white blood cell count or platelet count that has adverse implications in terms of the disease, if those are not adequately controlled. And then finally, if we’ve started cytoreductive therapy, did they adequately respond? Because if not, we know that they have higher risk. Individuals who have failed hydroxyurea have a decreased survival. They have a more difficult disease and need an appropriate change in therapy, which, according to our current guidelines, includes switching to ruxolitinib.
Transcript Edited for Clarity