Case 3: Management of Essential Thrombocythemia

Srdan Verstovsek, MD, PhD: Let’s open this case for discussion. I will start with the question about the need for the bone marrow biopsy. I try to make a case that it is needed, but there is a counterargument many times that the management of patients with prefibrotic myelofibrosis or ET [essential thrombocythemia]does not really differ much. It is really about the thrombotic risk assessment and yes or no of cytoreductive therapy. Andrew, what do you think about the need for bone marrow biopsies in patients, let’s say a 45-year-old with high platelets of 800,000 mm3? What would you look for and decide?

Andrew Kuykendall, MD: I think you’re right in the sense that it’s unlikely to change management, and I think that Rami talked about this a little bit in the discussion of polycythemia vera [PV]. But with ET, the problem is that just with the clinical sign of high platelets and maybe some molecular information, presuming a diagnosis of ET may be kind of looking at the rosy side of things. There’s a lot of things that can be seen on a bone marrow biopsy that will give you a better sense of what’s going on. So, I do prefer to get bone marrow biopsies on these patients, maybe not emergently, but certainly within the first year of diagnosis, to make sure that we’re truly dealing with ET, and it’s unlikely to change management. But these are patients who you’re likely going to be following (especially in your example of a 45-year-old) over the course of decades, and they’re likely to undergo different bone marrow biopsies and you’d like to have a baseline to compare it with.

Srdan Verstovsek, MD, PhD: Just quickly, is there really a need for periodic bone marrow biopsies in otherwise clinically stable patients with ET?

Andrew Kuykendall, MD: Absolutely not. I don’t recommend doing regular bone marrow biopsies in these patients. I often tell them the reason we’d ever do a bone marrow biopsy is if the disease changes or if there’s questions that we can’t answer just from the clinical situation and the blood work. So, no, not regularly, but certainly if the white blood cell count goes up or if there’s progressive anemia or other blood count concerns, then oftentimes, we will do another bone marrow biopsy.

Srdan Verstovsek, MD, PhD: Now, the introduction of the presence of 1 or the other driver mutations in our prognostication for thrombosis is relatively new. Prithviraj, is this something that we should really embrace, and should we also test for other mutations, not driver mutations in ET?

Prithviraj Bose, MD: Yes. To the first part, Srdan, I think so. I think the risk of thrombosis is largely restricted to JAK2, and at least the JAK2 CALR differentiation is important. I think less is known about the MPL mutation, we tend to cluster it with JAK2 and attribute similar characteristics. But it’s clear that the patients with the CALR mutation have a much lower risk, and it’s really the JAK2 that’s driving the thrombosis. So I think, yes, that is important and it affects management.

Regarding the second question, again, I think it goes back to what we discussed with PV. There’s been a number of genes, actually even more in ET than in PV, that have been implicated as being somewhat adverse. SRSF2 is the primary one. But, again, I don’t know that that affects management at this time, and I’m not sure that that should be a routine test for everyone. Again, it’s very important for research, though.

Transcript edited for clarity.