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Concept: Essential thrombocytosis


Evaluation of Xagrid® Efficacy and Long-term Safety, a Phase IV, prospective, non interventional study performed in 13 European countries enrolled high risk essential thrombocythemia patients treated with cytoreductive therapy. Primary objectives were safety and pregnancy outcomes. Of 3721 registered patients, 3649 received cytoreductive therapy. At registration, 3611 were receiving: anagrelide (Xagrid®) (n=804), other cytoreductive therapy (n=2666), anagrelide + other cytoreductive therapy (n=141). Median age was 56 vs 70 years for anagrelide vs other cytoreductive therapy. Event rates (patients with events/100 patient years) were, for total thrombosis 1.62 vs 2.06, venous thrombosis 0.15 vs 0.53. Anagrelide was more commonly associated with hemorrhage (0.89 vs 0.43), especially with anti-aggregatory therapy (1.35 vs 0.33) and myelofibrosis (1.04 vs 0.30). Other cytoreductive therapies were more associated with acute leukemia (AL) (0.28 vs 0.07) and other malignancies (1.29 vs 0.44). Post-hoc multivariate analyses identified increased risk for thrombosis with prior thrombohemorrhagic events, age ≥65, cardiovascular risk factors, or hypertension. Risk factors for transformation were prior thrombohemorrhagic events, age ≥65, time since diagnosis, and platelet count increase. Safety analysis reflected published data and no new safety concerns for anagrelide were found. Live births occurred in 41/54 pregnancies (76%). ( #NCT00567502).

Concepts: Scientific method, Blood, Observational study, Platelet, Multivariate statistics, Essential thrombocytosis, Phase IV, Anagrelide


Recombinant IFN-α (rIFN-α) induces complete hematologic remissions in patients with myeloproliferative neoplasms (MPNs), but its use has been limited by side effects owing to the relatively high doses used. Now, low-dose rIFN-α is stressed, starting relatively early in the course of the MPNs. In polycythemia vera, this has resulted in a significant clinical, hematologic, morphologic and molecular response manifested by reduction in the JAK2(V617F) allele burden, sustained even after discontinuation of recombinant IFN. In essential thrombocythemia, platelet count reduction is prompt and durable without treatment for varying periods. In hypercellular primary myelofibrosis, rIFN-α has restored normal blood counts, reduced splenomegaly and induced morphologic marrow remissions. This article highlights our current use of rIFN-α in MPNs.

Concepts: Blood, Red blood cell, Platelet, Hematology, Splenomegaly, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis


The recent discovery of mutations of the gene calreticulin has allowed raising the proportion of patients with essential thrombocythemia and primary myelofibrosis with known mutational abnormality up to 85-90%. Knowledge of the mechanisms by which mutated calreticulin underlie a myeloproliferative neoplasm as well as the clinical and therapeutic implications is just at the very beginning, and exciting times await research in this field.

Concepts: DNA, Cancer, Mutation, DNA repair, Point mutation, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis


Myeloproliferative neoplasms are clonal hematopoietic disorders that manifest as expansion of one or more myeloid lineages. The most common myeloproliferative neoplasms are chronic myeloid leukemia (CML), polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Whereas the genetic basis for CML has been known for more than 30 years, the specific genetic events that contribute to the pathogenesis of polycythemia vera, essential thrombocythemia, and primary myelofibrosis remained unknown until 2005. Our first insight into the molecular cause of these disorders came when the somatic JAK2 V617F mutation(1)-(4) was identified in the majority of patients with polycythemia vera and in a subset . . .

Concepts: Hematology, Leukemia, Acute myeloid leukemia, Blood disorders, Chronic myelogenous leukemia, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis


Vascular events represent the most frequent complications of thrombocytemias. We aimed to evaluate their risk in the WHO histologic categories of Essential Thrombocytemia (ET) and early Primary Myelofibrosis (PMF).

Concepts: Histology, Greek loanwords, Myelofibrosis, Essential thrombocytosis


Patients with Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or secondary prophylaxis. On the other hand, disease-related bleeding complications (i.e., from esophageal varices) are common in patients with MPN. This analysis was performed to define the frequency of such events, identify risk factors, and assess antiplatelet/anticoagulant therapy in a cohort of patients with MPN.

Concepts: Thrombosis, Actuarial science, Warfarin, Esophageal varices, Anticoagulant, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis


The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of these mutations has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for these mutations in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms.

Concepts: DNA, Diagnosis, Greek loanwords, World Health Organization, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis, Polycythemia vera


The discovery of the activating Janus kinase (JAK)2V617F mutation in 2005 in most patients with the classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) spurred intense interest in research into these disorders, culminating in the identification of activating mutations in MPL in 2006 and indels in the gene encoding calreticulin (CALR) in 2013, thus providing additional mechanistic explanations for the universal activation of JAK-signal transducer and activator of transcription (JAK-STAT) observed in these conditions, and the success of the JAK1/2 inhibitor ruxolitinib, which first received regulatory approval in 2011. The field has continued to advance rapidly since then, and the past 2 years have witnessed important changes to the classification of MPN and diagnostic criteria for polycythemia vera (PV), novel insights into the mechanisms of bone marrow fibrosis in primary myelofibrosis (PMF), increasing appreciation of the biologic differences between essential thrombocythemia (ET), prefibrotic and overt PMF, and between primary and post-PV/ET myelofibrosis (MF). Additionally, the mechanisms through which mutant CALR drives JAK-STAT pathway activation and oncogenic transformation are now better understood. Although mastocytosis is no longer included under the broad heading of MPN in the 2016 revision to the World Health Organization classification, an important milestone in mastocytosis research was reached in 2017 with the regulatory approval of midostaurin for patients with advanced systemic mastocytosis (AdvSM). In this article, we review the major recent developments in the areas of PV, ET, and MF, and also briefly summarize the literature on midostaurin and other KIT inhibitors for patients with AdvSM.

Concepts: Gene expression, Mutation, Signal transduction, Fibrosis, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis, Pancytopenia


The purpose of this study was to identify the incidence, causes and impact of non- adherence to oral and sub-cutaneous chronic treatments for patients with polycythaemia vera or essential thrombocythaemia. Patients receiving cytoreductive drugs for polycythaemia vera or essential thrombocythaemia were recruited at our institution (Observatoire brestois des néoplasies myéloprolifératives registry). They completed a one-shot questionnaire designed by investigators (étude de observance thérapeutique et des effets secondaires des traitements study). Data about complications (thrombosis, transformation and death) were collected at any time in the patient’s life (before diagnosis, up until consultation and after the completion of the questionnaire). Patients reported a poor adherence (<90%) in 22.7% of cases (65/286) for their cytoreductive drugs. Eighteen percent of the patients (46/255) also declared non-adherence to the antithrombotic drugs. In total, 85/286 patients (29.7%) declared to be non-adherent. Missing an intake is rare and is mostly due to forgetfulness especially during professional travels or holidays. Non-adherent patients were characterized by: younger age, living alone, having few medications but high numbers of pills and determining themselves their schedule of drug intake. Having experienced thrombosis or haematological evolution did not influence the adherence rate. Non-adherence to oral therapy was associated with a higher risk of phenotypic evolution (7.3 vs 1.8%, p=0.05). For patients treated for polycythaemia vera or essential thrombocythaemia, non-adherence to cytoreductive and/or antithrombotic therapies is frequent, influenced by age, habitus and concomitant treatments, but not by disease history or treatment side effects. Phenotypic evolutions seem to be more frequent in the non-adherence group. ( #NCT02893410, #NCT02897297).

Concepts: Pharmacology, Medicine, Evolution, Red blood cell, Illness, Hematology, Essential thrombocytosis, Polycythemia


Myeloproliferative neoplasms (MPNs) are chronic blood disorders caused by clonal expansion in one or more myeloid lineages and include essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF) and chronic myeloid leukemia (CML). Cardiovascular events are a main challenge for patients with MPN and can lead to their death.

Concepts: Blood, Hematology, Leukemia, Blood disorders, Chronic myelogenous leukemia, Myeloproliferative disease, Myelofibrosis, Essential thrombocytosis