How we diagnose and treat essential thrombocythaemia

Abstract

SummaryThe approach to the diagnosis and management of essential thrombocythaemia (ET) is steadily changing, influenced by advances in molecular biology, data from clinical trials and retrospective analyses of patient cohorts. In the past decade options for clinical management largely remain unchanged, but who we treat, and with what target in mind, is evolving. A further area of change is recognition of symptoms that may be associated with ET, as well as other myeloproliferative neoplasms, and that potential options for their management are becoming available. Judicious and careful diagnosis is increasingly a fundamental key to successful management followed by cytoreductive therapy in a subset of patients. In this review we demonstrate our management strategies for ET using a case-based format.

Ruxolitinib vs best available therapy for ET intolerant or resistant to hydroxycarbamide

“…5 In addition, disease-related symptom burden is increasingly recognized as an important disease feature, causing significant morbidity with few effective treatments. [2][3][4] In previous studies, patients with MF gained a survival benefit with ruxolitinib, which also reduced spleen size and symptoms compared with BAT. 14 In the RESPONSE study in HCresistant/intolerant PV patients, there was a suggestion of lower rates of thrombosis in patients receiving ruxolitinib compared with BAT as well as better control of blood counts, spleen size, and symptoms.…”

“…2,3 Criteria for resistance or intolerance to therapy with HC were originally developed to guide clinicians when to initiate second-line therapies; however, there is now evidence that HC-resistant patients have a poor outlook. 5 In addition, disease-related symptom burden is increasingly recognized as an important disease feature, causing significant morbidity with few effective treatments.…”

“…5 No prospective trial data exist to guide management of ET patients who are HC resistant or intolerant; treatment options are limited, and several second-line treatment options are associated with increased risk of disease transformation. 2,3,6 The discovery of the Janus kinase (JAK2V617F) mutation provided the first genetic marker of the malignant clone in MPN. [7][8][9] Furthermore, other key driver mutations associated with ET, affecting thrombopoietin receptor MPL and calreticulin (CALR), also led to increased JAK2 signaling.…”

Spotlight on anagrelide hydrochloride for the treatment of essential thrombocythemia

“…But there are still considerable concerns regarding reproducibility and different histopathologists being able to clearly distinguish between the two entities, as discussed earlier. 10,13,19 Nonetheless, the proposal that treatment recommendations for WHO-ET may not apply to patients with PVSG-ET is intriguing. However, the non-inferiority design of the ANAHYDRET study is a clear limitation with inadequate statistical power to permit universal treatment recommendations.…”

“…Experimental therapies currently being explored in ET include JAK inhibitors, histone deactylase inhibitors and the telomerase inhibitor imetelstat. 19 This review is an update on studies evaluating the use of ANA in the treatment of thrombocytosis in the context of MPNs with particular emphasis on its use in high-risk ET. Current evidence suggests an important role of ANA in the treatment of individuals for whom HC is inappropriate or inadequate, or might be associated with long-term toxicity, such as younger patients.…”