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Background. The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group). Objectives. To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis. Materials and methods. The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis. Results. Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85--89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy. Conclusions. We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population. [ABSTRACT FROM AUTHOR]

Polycythemia vera (PV) belongs to a group of myeloproliferative neoplasms (MPN). The diagnosis of PV is based on the evaluation of complete blood count, bone marrow trephine biopsy samples, and molecular tests (confirmation of the JAK2 mutation). The main objectives of PV treatment include preventing thromboembolic complications, alleviating disease symptoms, and lowering the risk of transformation to myelofibrosis, acute myeloid leukemia and myelodysplastic syndrome. Taking into consideration the long-term course of PV, the choice of therapy should be based on an analysis of the risks resulting from the disease as well as from the adverse effects of the medication applied. In patients without risk factors (age <60 years; no history of thrombosis), acetylsalicylic acid (ASA) and phlebotomy are recommended. Cytoreductive treatment is recommended in patients with poor tolerance of phlebotomy and with leukocytosis >20 G/L, symptomatic progressive splenomegaly, significant thrombocytosis, persistent general symptoms of PV, and also in patients with significant cardiovascular risk. The therapy of choice in these patients is interferon α (IFNα). In a high-risk group of patients, (age ≥60 years and/or a history of thrombosis), treatment with ASA and phlebotomy should be accompanied by cytoreduction: hydroxyurea (HU) or, in the case of HU resistance/intolerance, ruxolitinib (RUX) or IFNα. This paper discusses some aspects of the risk evaluation and summarizes the effectiveness of the available therapies, and also presents diagnostic and therapeutic recommendations for PV. [ABSTRACT FROM AUTHOR]

Introduction: Polycythemia vera (PV) and essential thrombocythemia (ET) are diseases driven by canonical mutations in JAK2, CALR, or MPL gene. Previous studies revealed that in addition to driver mutations, patients with PV and ET can harbor other mutations in various genes, with no established impact on disease phenotype. We hypothesized that the molecular profile of patients with PV and ET is dynamic throughout the disease. Methods: In this study, we performed a 37-gene targeted next-generation sequencing panel on the DNA samples collected from 49 study participants in two-time points, separated by 78-141 months. We identified 78 variants across 37 analyzed genes in the study population. Results: By analyzing the change in variant allele frequencies and revealing the acquisition of new mutations during the disease, we confirmed the dynamic nature of the molecular profile of patients with PV and ET. We found connections between specific variants with the development of secondary myelofibrosis, thrombotic events, and response to treatment. We confronted our results with existing conventional and mutation-enhanced prognostic systems, showing the limited utility of available prognostic tools. Discussion: The results of this study underline the significance of repeated molecular testing in patients with PV and ET and indicate the need for further research within this field to better understand the disease and improve available prognostic tools. [ABSTRACT FROM AUTHOR]

Introduction and objectives: The most common mutation within the spectrum of myeloproliferative neoplasms (MPNs) is a mutation in Janus kinase 2 gene (JAK2V617F). It has been observed that, during a course of disease, transformation from JAK2‐mutated essential thrombocythemia (ET) to overt polycythemia vera (PV) can occur. Primary objective of this study was to show the incidence of mentioned phenomenon. Methods: In this study, we analyzed data of 136 patients diagnosed with JAK2‐positive ET observed for a median time of 9 years. We examined blood count of each patient at the time of diagnosis and confronted it with 2008 and 2016 WHO criteria for PV and mPV. Additionally, we analyzed JAK2V617F allele burden in two separate time points among selected cases. Results: Confrontation with new criteria resulted in change of diagnosis to PV and mPV in 10% and 9% cases, respectively. Within remaining patients, 14 showed increasing hemoglobin concentration over several months during late course of disease, resulting in change of diagnosis to overt PV. We did not find suggested increase in JAK2 allele burden among transforming patients. Conclusions: Phenotype transformation to polycythemia was proven to be possible within the group of JAK2‐mutated ET; however, cause of this effect remains uncertain. [ABSTRACT FROM AUTHOR]

According to the current treatment recommendations, anagrelide, an oral antiplatelet agent, is recommended as a second-line therapy for patients with high-risk essential thrombocythemia experiencing intolerance or refractoriness to first-line approach, such as hydroxyurea or pegylated interferon alpha-2a. If there is a need for the introduction of cytoreductive treatment in young patients, with a perspective of lifelong exposure, both the efficacy and long-term outcomes should be known. We present the analysis of 48 young patients, diagnosed with essential thrombocythemia below the age of 60, who were exposed to anagrelide treatment for over 10 years. Our observations show that the highest proportion of complete remissions without adverse events and disease progression is seen in the JAK2-mutated patients. Additionally, by evaluating the changes in hemoglobin concentration and serum erythropoietin throughout the study, we were able to reveal the development of diminished susceptibility to erythropoietin as a driving factor of the anemia in patients treated with anagrelide. The pro-anemic effect was most pronounced, and sustained, in patients harboring CALR mutation. In summary, we recommend the preferred use of anagrelide in JAK2-mutated patients diagnosed with essential thrombocythemia and limiting the exposure time. [ABSTRACT FROM AUTHOR]