Case Studies in Myeloproliferative Neoplasms - Episode 16

Case 3: Risk Assessment in ET

Dr Stephen Oh discusses risk assessment in patients with essential thrombocythemia.

Stephen Oh, MD, PhD: When we think about ET [essential thrombocythemia] and risk, much of our consideration would be focused on the risk of thrombosis. For many years, there has been a simple approach to categorizing patients in terms of risk of thrombosis. It’s identical to what has been used historically for polycythemia vera, which is utilizing simply 2 risk factors: age greater than 60 and a previous history of thrombosis. Absence of either of those risk factors would put patients in a low-risk group, and presence of 1 or both of those risk factors would put them in a high-risk group.

Patients who have extreme thrombocytosis, defined as a platelet count greater than 1,500,000 per mm3, is a unique situation. If anything, there might be more of an association with increased risk of bleeding. Otherwise, we don’t specifically factor the degree of thrombocytosis into the consideration of risk of thrombotic complications. In the past 5 years or so, with the identification of the CALR mutation that’s present in a proportion of patients with ET, it has been well established that those patients with ET who are CALR-mutated have a lower risk of thrombosis. We already knew this to some extent. We just used to call these patients JAK2-negative, but now we know the majority of these patients with JAK2-negative ET are in fact mutated for CALR. These patients have a lower risk of thrombosis. That information can now be considered in terms of a revised approach to risk stratification for thrombosis.

The revised IPSET [International Prognostic Score for Thrombosis in Essential Thrombocythemia] thrombosis score is now commonly used in the field and is essentially endorsed by the NCCN [National Comprehensive Cancer Network] guidelines for ET. Along with the 2 traditional risk factors, age greater than 60 and previous history of thrombosis, this adds 1 more factor, which is JAK2-mutation positive. This is not exactly the same as JAK2-positive vs CALR-positive, because not every patient who is JAK2-negative is CALR-positive. Rather, if the JAK2 mutation is present, that is associated with a higher risk of thrombosis compared with those who do not have the mutation. When you use those 3 risk factors, patients can be placed into 4 different risk groups instead of the simple 2 in the past. Then you can create a little more precision in terms of these categories. If a patient has none of these 3 risk factors, they would be considered very low risk. If their only risk factor is a JAK2 mutation, then they’re low risk. If their only risk factor is age greater than 60, they’re intermediate risk. If they have either a prior history of thrombosis or advanced age greater than 60 and the presence of a JAK2 mutation, they’re in the high-risk category.

This not only adds a little more precision in terms of risk of thrombosis, but it can also potentially impact choice of treatment in a more refined way than in the past. For instance, patients in the very low-risk category have no risk factors. While we generally have traditionally thought that all patients with ET should be placed on treatment of aspirin, we can now at least consider the possibility that these patients are at such low risk for thrombosis that aspirin may not be beneficial. In fact, it could be harmful in terms of risk of bleeding. In particular, patients in that category who had that very high platelet count may be at high risk for bleeding. Furthermore, in the past, patients in that intermediate-risk category whose only risk factor is age greater than 60 were often placed in the high-risk category based on that 1 risk factor, and therefore cytoreductive therapy would be recommended. Now we can say that they’re not as high risk as that higher risk category, so is cytoreductive therapy truly indicated? There’s a little more subtlety to approaching both prognosis and treatment options. These risk categories and approaches to treatment are now largely reflected in the updated NCCN guidelines for treatment of patients with ET.

This transcript has been edited for clarity.