Essential Thrombocythemia: An Overview


Expert discusses risk-stratification models, prognosis, and the management of complications in essential thrombocythemia.

Pankit Vachhani, MD: There are various risk stratification models in essential thrombocytosis. Largely speaking, one may want to think of these in terms of risk stratification for survival vs risk for thrombosis. The first of which was IPSET [International Prognostic Score for Thrombosis in Essential Thrombocythemia] and the IPSET thrombosis models. The IPSET thrombosis model then further underwent revision, and the result was the revised IPSET thrombosis model. I should mention, as an NCCN [National Comprehensive Cancer Network] panel member, that we at the NCCN panel have adopted the revised IPSET thrombosis model within the NCCN Guidelines for myeloproliferative neoplasms as well.

Now, the revised IPSET thrombosis risk-stratification scheme divides the essential thrombocytosis into 4 major risk categories. These are very low-risk ET [essential thrombocytosis], low-risk ET, intermediate-risk ET, and high-risk ET. This is largely done based on 3 risk factors. One is less than or more than 60 years of age, the presence or absence of JAK2 mutations, and the third is the history of thrombocytosis. A low-risk category would be anyone who is less than 60 years of age, does not have JAK2 mutation and has had no prior history of thrombosis. Low-risk thrombosis or low-risk ET would be a category where those who are less than 60 years of age had no prior history of thrombosis but have JAK2 mutation.

Intermediate-risk ET would be age more than 60 years of age, no JAK2 mutation, and no prior history of thrombosis. Crucial to note is the high-risk category and any history of thrombosis at any age would put anyone in a high-risk category. Or being 60 years of age or more and having a JAK2 mutation would lead to the classification under high-risk essential thrombocytosis.

When we think about prognosis for essential thrombocytosis, we typically think about thrombosis-related prognosis, not so much survival-related prognosis. This is because the prognosis for essential thrombocytosis patients is vastly similar, maybe slightly inferior to age-matched and sex-matched control populations. For survival one may refer to either the original IPSET classification or the relatively new MIPSSET, which is the molecularly enhanced IPS for essential thrombocytosis classification.

Within MIPSSET, the patients can be divided into low-, intermediate-, or high-risk ET. Those who are low risk by MIPSSET classification have a survival probably more than 30 years of age, based on the data that we have. Those who are intermediate have about 14 years. Those who are high risk have a median survival of around 8 years.

When I approach the complications of essential thrombocytosis, I divide these into thrombosis-related complications, leading related complications and complications in the form of progression to more aggressive malignancies. Within the category of thrombosis-related complication, one should note that the arterial thrombosis is found at a high rate, almost a 2:1 ratio compared with venous thrombosis. In 1 study, for example, 14% of patients had arterial thrombosis prior to or at the time of diagnosis of essential thrombocytosis. One, for that same population, about 8% of them had renal thrombosis. In the same population, that was followed for 10 years subsequently 15% additional patients had arterial thrombosis when only 8% had renal thrombosis.

In the same population that was followed for 10 more years, about 15% additional patients had arterial thrombosis vs 8% with renal thrombosis. When it comes to bleeding we typically think of gastrointestinal bleeding. That is actually the most common cause of major bleeding in patients with essential thrombocytosis. About 4% have had it prior to or at the time of their diagnosis of essential thrombocytosis. About 6% more may have it after the diagnosis of essential thrombocytosis.

With regard to the additional complication, one thinks about progression to myelofibrotic phase of essential thrombocytosis. That occurs in about 1% to 5% of the population, depending on the studies we look at. Around 1% to 2% of patients may progress to a blastic phase of their disease, generally referred to as acute myeloid leukemia or plastic phase of essential thrombocytosis. The risk factors for progression to acute myeloid leukemia have included things like anemia, platelet count of more than 1 million per mm3, and even the presence of TP53 mutation.

Risk factors for progression to myeloid fibrotic phase of essential thrombocytosis are advanced age, anemia, presence of JAK2 V6 mutation, it has responded to a lower risk of progression to fibrotic stage. But in the new MIPSSET model, presence of spliceosome mutations has been shown to correlate with a higher risk of progression to overt myeloma fibrosis.

Transcript edited for clarity.

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