Clinical Pearls & Morning Reports
Published November 27, 2019
The major treatment objective in patients with essential thrombocythemia is prevention of vascular events. Read the Clinical Practice article here.
Q: What genes harbor the driver mutations associated with essential thrombocythemia?
A: The majority of patients with essential thrombocythemia (approximately 60%) express the JAK2 V617F mutation, whereas the remainder harbor the mutations in CALR (approximately 20%) or MPL (approximately 3%) or none of the three driver mutations (10 to 20% are triple-negative).
Q: Does essential thrombocythemia have a poor prognosis?
A: Despite having a higher risk of death than the general population, patients with essential thrombocythemia, especially those with morphologically confirmed disease, have life expectancies that are only slightly lower than those of persons without the disease and generally better than those of patients with other myeloproliferative neoplasms.
A: Conventional risk factors for thrombosis in essential thrombocythemia are age greater than 60 years and a history of thrombosis. Recent studies have identified additional risk factors; the revised International Prognostic Score for Essential Thrombocythemia (IPSET) model takes into account conventional risk factors as well as the presence of the JAK2 V617F mutation and cardiovascular risk factors to categorize patients into four groups according to level of risk. In patients with conventionally low risk, the absence of the JAK2 V617F mutation and cardiovascular risk factors defines “very-low-risk disease.” The presence of JAK2 V617F is associated with a significantly increased risk of thrombosis (categorized as “low risk”). Patients older than 60 years of age who have neither a history of thrombosis nor the JAK2 V617F mutation are considered to be at “intermediate risk”; their risk of thrombosis is significantly lower than that of patients at “high risk,” who have a history of thrombosis or the JAK2 V617F mutation.
A: Limited data from controlled trials are available to guide selection of therapy in patients with high-risk essential thrombocythemia. Although not approved by the Food and Drug Administration for this indication, hydroxyurea is the most frequently prescribed first-line drug for patients with essential thrombocythemia given its ease of administration, good profile regarding efficacy and side effects, and low incidence of treatment resistance. Possible exceptions to the use of hydroxyurea include younger patients (<40 years of age), particularly women of childbearing age, owing to concerns regarding gonadal toxicity and mutagenicity. Hydroxyurea also has teratogenic and embryotoxic effects and is consequently not considered safe for use during pregnancy.