Case Studies in Myeloproliferative Neoplasms - Episode 17

Case 3: Individualized Therapy for ET

Experts in essential thrombocythemia discuss approaches to individualizing therapy.

Stephen Oh, MD, PhD: I want to briefly mention this category of triple-negative ET [essential thrombocythemia]. We have the JAK2, CALR, and MPL mutations that comprise roughly 80% to 85% of patients with ET. That leaves at least 10% to 15% or more of patients with ET who are negative for JAK2, MPL, and CALR mutations. This is a very difficult category to grapple with in the case of ET in particular, because now there could be some consideration for asking whether this is truly ET. We have the WHO [World Health Organization] criteria. We can perform a bone marrow biopsy and look for the characteristic changes. We always initially approach thrombocytosis, in terms of the work-up, with the question of whether this could actually be a reactive thrombocytosis. Is this truly a clonal disorder? When you don’t have a JAK2, MPL, or CALR mutation to hang your hat on, in my approach, I always come back to asking, is this in fact ET, or did I miss something in the work-up?

Let’s say you are confident this really is ET, and they’re in the triple-negative category. What does that mean? It’s a bit of a dilemma in terms of what to expect for these patients. My view is that it is a mixed bag. It’s a heterogeneous group of patients. Some patients are going to do very well, while others may have something that makes them unique in this category. Each patient thus needs to be approached individually within that category.

What about patients who are between the ages of 40 and 59 and in that intermediate- to low-risk category? They’re not quite 60. They do not have any other high-risk features. Should we consider being more aggressive and initiating cytoreductive therapy? This has been studied, and the long story short is that, in comparing patients put on aspirin vs hydroxyurea plus aspirin, the outcomes were not better in patients who had the additional cytoreductive therapy. This reinforces that there is no indication for the addition of cytoreductive therapy in this risk group specifically.

I want to talk for a minute about post-ET myelofibrosis [MF]. This connects back to part of our discussion about myelofibrosis. Within a subset of patients who have ET, there is concern that they may be progressing to myelofibrosis. One of the challenges is that the exact point where that crossover from ET to myelofibrosis occurs is not always straightforward. Another way to say it is to question whether there really is a clear demarcation. I will often say to patients is that it’s more of a continuum, and we don’t have to say at any given time it’s either ET or myelofibrosis. It could be anywhere in between.

With that said, there are specific diagnostic criteria that have been developed by the IWG-MRT [International Working Group–Myeloproliferative Neoplasms Research and Treatment] for post-ET myelofibrosis. These include: No. 1, a previous diagnosis of ET; No. 2, grade 2 or 3 bone marrow fibrosis. That would be the 2 required criteria. Then you need at least 2 of the additional minor criteria, including the development of anemia, leukoerythroblastic peripheral smear, new or increasing palpable splenomegaly, constitutional symptoms, or increased LDH [lactate dehydrogenase]. All of those things are commonly seen in myelofibrosis. When we fear a patient with ET is progressing to MF, these are things you can look for to support that transition.

This transcript has been edited for clarity.