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Myeloproliferative neoplasms are rare in childhood. They are categorized as Philadelphia chromosome-positive and Philadelphia chromosome-negative. Chronic myeloid leukemia (CML) is the most common myeloproliferative disease in which the Philadelphia chromosome is detected as a result of BCR-ABL rearrangements. In others, the most common genetic abnormality is JAK2V617F mutation. The coexistence of these 2 abnormalities in CML is unexpected, and rare cases have recently been reported in adults. We present a child who had a very high platelet count in which we found this coexistence. The clinical presentation, laboratory findings, management, and prognosis of this coexistence is challenging in such a rare condition. [ABSTRACT FROM AUTHOR]

Background Thrombotic complications are the most considerable etiology causing morbidity and mortality in patients with philadelphia (Ph) negative myeloproliferative neoplasms (MPN). There are many studies evaluating the association of JAK2 mutation and risk of thrombosis in MPN with inconclusive results. We also investigated the relation between JAK2 mutation in all Ph negative MPN and thrombosis. Material and Methods Thrombotic events and demographic features of 177 patients with Ph negative MPN were evaluated retrospectively. Results JAK2 V617 F mutation was detected in 57% of patients with essential thrombocythemia (ET), %90.3 of pateints with polycythemia vera (PV), 100% of pateints with primary myelofibrosis (PMF). Thrombotic complications occured more frequently with JAK2 mutation in all MPN patients than without (p=0.014). In JAK 2 mutation positive groups, the median age, thrombosis risk scores and leucocyte values are higher, splenomegaly and arterial and/or venous thrombosis are detected more frequently (p<0.05). In subgroup analysis, there is a significant difference found in JAK 2 positive ET patients and negative group in case of thrombosis (p=0.023). Conclusions JAK2 mutation and monitoring for thrombotic events should be performed in all MPN patients. [ABSTRACT FROM AUTHOR]

Lack of demonstrable mutations affecting JAK2, CALR, or MPL driver genes within the spectrum of BCR-ABL1-negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5–10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the TET2 gene (55.0%), followed by KIT (27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted.

Lack of demonstrable mutations affecting JAK2, CALR , or MPL driver genes within the spectrum of BCR-ABL1 -negative myeloproliferative neoplasms (MPNs) is currently referred to as a triple-negative genotype, which is found in about 10% of patients with essential thrombocythemia (ET) and 5–10% of those with primary myelofibrosis (PMF). Very few papers are presently available on triple-negative ET, which is basically described as an indolent disease, differently from triple-negative PMF, which is an aggressive myeloid neoplasm, with a significantly higher risk of leukemic evolution. The aim of the present study was to evaluate the bone marrow morphology and the clinical-laboratory parameters of triple-negative ET patients, as well as to determine their molecular profile using next-generation sequencing (NGS) to identify any potential clonal biomarkers. We evaluated a single-center series of 40 triple-negative ET patients, diagnosed according to the 2017 WHO classification criteria and regularly followed up at the Hematology Unit of our Institution, between January 1983 and January 2019. In all patients, NGS was performed using the Illumina Ampliseq Myeloid Panel; morphological and immunohistochemical features of the bone marrow trephine biopsies were also thoroughly reviewed. Nucleotide variants were detected in 35 out of 40 patients. In detail, 29 subjects harbored one or two variants and six cases showed three or more concomitant nucleotide changes. The most frequent sequence variants involved the TET2 gene (55.0%), followed by KIT (27.5%). Histologically, most of the cases displayed a classical ET morphology. Interestingly, prevalent megakaryocytes morphology was more frequently polymorphic with a mixture of giant megakaryocytes with hyperlobulated nuclei, normal and small sized maturing elements, and naked nuclei. Finally, in five cases a mild degree of reticulin fibrosis (MF-1) was evident together with an increase in the micro-vessel density. By means of NGS we were able to identify nucleotide variants in most cases, thus we suggest that a sizeable proportion of triple-negative ET patients do have a clonal disease. In analogy with driver genes-mutated MPNs, these observations may prevent issues arising concerning triple-negative ET treatment, especially when a cytoreductive therapy may be warranted. [ABSTRACT FROM AUTHOR]

Major disease complications for patients with essential thrombocythemia (ET) include thrombosis and fibrotic or leukemic transformation. Calreticulin (CALR) mutation type 1 frequencies in ET are estimated between 7% and 11% and ET patients carrying CALR type 1 mutation are associated with lower risk of thrombosis but higher risk of myelofibrosis transformation compared to ET patients with JAK2 mutation. Leukemic transformation rates at 20 years are estimated at less than 5% for ET and risk factors for leukemic transformation are advanced age, thrombosis history, leukocytosis, and anemia. Amongst the subtypes of blast phase myeloproliferative neoplasms, acute promyelocytic leukemia is extremely rare. Herein, we present a case of a promyelocytic blast crisis of post-ET myelofibrosis with associated life-threatening splanchnic vein thrombosis. This case suggests that inflammation plays a key role in thrombotic events and fibrotic/leukemic transformation in ET patients, regardless the molecular landscape.

Mastocytosis is a rare disease that has been defined as an abnormal accumulation of mast cells in one or more organ systems. Previously considered a myeloproliferative neoplasm, mastocytosis is now classified in its own category under myeloid neoplasms. Since 2016 it was separated into three categories, cutaneous mastocytosis (CM), systemic mastocytosis (SM) and mast cell sarcoma, these diseases occuring in both children and adults. We hereby present a diagnostic algorithm and a short case report of a patient with a rare form of SM. [ABSTRACT FROM AUTHOR]

Background: Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) typically incur high rates of infections and both drugs and comorbidities may modulate infection risk., Objectives: The present study aims to assess the effect of immunosuppressive agents on clinical outcomes of MPN patients affected by the coronavirus disease 2019 (COVID-19)., Design: This is an observational study., Methods: We specifically searched and analyzed MPN patients collected by EPICOVIDEHA online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020., Results: Overall, 398 patients with MPN were observed for a median of 76 days [interquartile range (IQR): 19-197] after detection of SARS-CoV2 infection. Median age was 69 years (IQR: 58-77) and 183 individuals (46%) had myelofibrosis (MF). Overall, 121 patients (30%) of the whole cohort received immunosuppressive therapies including steroids, immunomodulatory drugs, or JAK inhibitors. Hospitalization and consecutive admission to intensive care unit was required in 216 (54%) and 53 patients (13%), respectively. Risk factors for hospital admission were identified by multivariable logistic regression and include exposure to immunosuppressive therapies [odds ratio (OR): 2.186; 95% confidence interval (CI): 1.357-3.519], age ⩾70 years, and comorbidities. The fatality rate was 22% overall and the risk of death was independently increased by age ⩾70 years [hazard ratio (HR): 2.191; 95% CI: 1.363-3.521], previous comorbidities, and exposure to immunosuppressive therapies before the infection (HR: 2.143; 95% CI: 1.363-3.521)., Conclusion: COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals., Plain Language Summary: EPICOVIDEHA registry reports inferior outcomes of COVID-19 in patients with Philadelphia-negative chronic myeloproliferative neoplasms receiving immunosuppressive therapies. Patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPN) incur high rates of infections during the course of their disease.The present study was aimed at assessing which patient characteristics predicted a worse outcome of SARS-COV-2 infection in individuals with MPN.To pursue this objective, the researchers analyzed the data collected by EPICOVIDEHA, an international online registry, which includes individuals with hematological malignancies diagnosed with COVID-19 since February 2020.The database provided clinical data of 398 patients with MPN incurring COVID-19:Patients were mostly elderly (median age was 69 years);Forty-six percent of them were affected by myelofibrosis, which is the most severe MPN;Moreover, 32% were receiving immunosuppressive therapies (JAK inhibitors, such as ruxolitinib, steroids, or immunomodulatory IMID drugs, such as thalidomide) before COVID-19.Hospitalization was required in 54% of the patients, and the risk of being hospitalized for severe COVID-19 was independently predicted byOlder age;Comorbidities;Exposure to immunosuppressive therapies.Overall, 22% of MPN patients deceased soon after COVID-19 and the risk of death was independently increased over twofold byOlder age;Comorbidities;Exposure to immunosuppressive therapies before the infection.In conclusion, COVID-19 infection led to a particularly dismal outcome in MPN patients receiving immunosuppressive agents, including JAK inhibitors, or reporting multiple comorbidities. Therefore, specific preventive strategies need to be tailored for such individuals., Competing Interests: The author declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSG reports speaker honoraria from Gilead and Pfizer, outside of the submitted work. DW received speakers honorary and research funding from Novartis, AOP Pharma, Incyte, Bexxalta, BMS/Celgene, outside of the submitted work. MM received consultancy fees from Gilead, outside of the submitted work. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Abbvie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, Pardes, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, PSI, Pulmocide, Shionogi; A patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7), outside of the submitted work. No relevant conflicts of interest are reported by all the other authors., (© The Author(s), 2023.)

Essential thrombocytemia is a classic negative chronic myeloproliferative disease BCR-ABL characterized by global myeloid proliferation but mainly on the megacariocitary series. Most symptomatic patients show manifestations due to the vascular thromboses or haemorrhages. The objective of the paper is to evaluate the incidence of thrombotic complications. The study was carried out in the Haematology Compartment of Constanta County Clinical Hospital on a lot of 60 cases with essential thrombocytemia. The diagnosis criteria were OMS 2008 criteria. On the studied lot, on the diagnosis, 45 patients (75%) were symptomatic. Among the symptomatic ones 27 patients (60%) showed thromboembolic manifestations in the moment of the diagnosis or after diagnosis. The thrombotic manifestations present at the patients with essential thrombocytemia taken for the study were: cerebral micro thromboses - 10 cases; peripheral micro thromboses - 3 cases; erythromelalgia - 6 cases; acrocyanosis - 2 cases; coronary thrombosis - 1 case; portal vein thrombosis - 2 cases; pulmonary thromboembolism - 1 case; thrombosis of placenta vessels- 2 cases. The thrombocytosis degree is not the only important risk factor for thrombosis. The age over 60 years, arterial hypertension, dyslipidemia, smoking, atherosclerosis, are associated risk factors (independent from thrombocytosis) for the frequency and severity of the thromboses. In this framework, on the one hand the increase of accessibility to the background therapy proven efficient (interferon, anagrelide) and on the other hand the mentioning in the cardiovascular pathology guides of primary and secondary thromboses as risk factors along with hypertension, diabetes, dyslipidemias, etc is required. [ABSTRACT FROM AUTHOR]

Background: 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). Methods: From our clinical database of 283 thrombocytemic patients, we selected those with available bone marrow histology performed before any treatment, at or within 1 year from diagnosis, and reclassified the 131 cases as true ET or early PMF, with or without fibrosis, according to the WHO histological criteria. Vaso-occlusive events at diagnosis and in the follow-up were compared in the WHO-groups. Results: Histologic review reclassified 61 cases as ET and 72 cases as early PMF (26 prefibrotic and 42 with grade 1 or 2 fibrosis). Compared to ET, early PMF showed a significant higher rate of thrombosis both in the past history (22% vs 8%) and at diagnosis (15.2% vs 1.6%), and an increased leukocyte count (8389 vs 7500/mmc). Venous thromboses (mainly atypical) were relatively more common in PMF than in ET. Patients with prefibrotic PMF, although younger, showed a significant higher 15-year risk of developing thrombosis (48% vs 16% in fibrotic PMF and 17% in ET). At multivariate analysis, age and WHO histology were both independent risk-factors for thrombosis during follow-up; patients >60 yr-old or with prefibrotic PMF showed a significantly higher risk at 20 years than patients <60 yr-old with ET or fibrotic PMF (47% vs 4%, p = 0.005). Conclusions: Our study support the importance of WHO histologic categories in the thrombotic risk stratification of patients with thrombocytemias. [ABSTRACT FROM AUTHOR]

Abstract: The aims of this present study were to: 1) assess the characteristics of hematological malignancies in polymyositis/polymyositis (PM/DM) patients; and 2) determine predictive variables of hematological malignancies in PM/DM patients. We retrospectively reviewed the medical records of 32 patients (14 PM, 18 DM) associated with hematological malignancies. In our 32 PM/DM patients, hematological malignancy was concurrently identified (18.8%) or occurred during the course of PM/DM (31.2%); although, PM/DM more often preceded hematological malignancy onset (50%). We observed that the types of hematological malignancies varied, consisting of: B-cell lymphoma (n=20), T-cell lymphoma (n=4), Hodgkin''s disease (n=2), multiple myeloma (n=1), myelodysplastic syndrome without excess of blasts (n=3), hairy cell (n=1) and acute lymphocytic leukemia (n=1). In 21 patients of our 32 patients with PM/DM-associated hematological malignancy (65.6% of cases), PM/DM paralleled the course of hematological malignancy. Finally, we observed that patients with PM/DM-associated hematological malignancies had a poor prognosis, the survival status ranging from 96.9%, 78.1% and 51.4% at 1, 3 and 5years, respectively. Interestingly, we found that patients with hematological malignancies, compared with those without were older and more frequently had DM; on the other hand, these patients less commonly exhibited: joint involvement (p=0.017), interstitial lung disease (p=0.06) and anti-Jo1 antibody (p=0.001). Taken together, our study underscores that the association between PM/DM and hematological malignancy, especially lymphoma, should not be ignored. Our findings also suggest that antisynthetase syndrome may be a protective factor of hematological malignancy in PM/DM patients. [Copyright &y& Elsevier]

In this study, we planned to investigate frequency of the JAK2 V617F mutation and it's relation with clinical and laboratory findings of BCR-ABL negative myeloproliferative diseases (MPD) which consist of polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Totally 65 patients were included in the study which composed of 28 (43.1 %) PV, 29 (44 %) ET and 8 (12.3 %) IMF patients. Forty one (63%) patients were female and 24 (37%) were male. Mean age of patients was 64.02±12.42. Frequency of the JAK2V617F mutation was found in 25 (89.3%) of PV, 18 (62.1%) of ET and 2 (25%) of IMF patients. We found no difference in gender and frequency of thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow fibrosis, cytoreductive treatment requirement, arterial/venous thrombosis between JAK2 V617F mutated and unmutated PV and ET and IMF patients. When compared homozygous and heterozygous JAK2 V617F mutated PV and ET patients according to these variables, there was no significant difference. There were no statistically significant difference in Hemoglobin (Hb), hematocrit (HCT), leukocyte, lactate dehidrogenase (LDH), EPO and ferritin levels between JAK2 V617F mutated and unmutated PV and ET patients. HCT levels and leukocyte counts were significantly higher in JAK2 V617F mutated than unmutated IMF patients (p=0.046, p=0.046). Other variables were not found different. Comprehensive prospective studies are necessary for determining the relationship of the JAK2 V617F mutation with clinical and laboratory findings . [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Bone marrow necrosis is a very rare condition which is characterized by a necrosis of hematopoietic progenitors, adipocytes and reticulin network. Case report: We report a 62-year-old woman admitted to an intensive care unit for an essential thrombocytemia associated with bone marrow necrosis complicated by septic shock and progressive multi-organ failure. To our knowledge, this is the second case reported in the literature. The clinical presentation of bone marrow necrosis includes non-specific symptoms such as fever, bone pain and sometimes a clinically significant medullar insufficiency syndrome. Biology can reveal cytopenias, elevated LDH and alkaline phosphatase serum levels. The diagnosis is confirmed by bone marrow trephine biopsy. Bone marrow necrosis is classified as extensive if more than 50% of the bone marrow biopsy show necrosis. Haematological malignancies (particularly leukaemia), and solid malignant tumours (particularly gastro-intestinal or lung cancers) represent up to 90% of aetiologies and must be actively researched. Also, sickle cell disease and catastrophic anti-phospholipid syndrome must also be investigated. Essential thrombocytemia remains an exceptional cause of bone marrow necrosis. Conclusion: Overall the prognosis of bone marrow necrosis is poor unless appropriate and intensive treatment, especially for sickle cell disease in which complete medullar regeneration has been observed. [Copyright &y& Elsevier]

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Abstract: Objective: To evaluate the management and outcome of pregnancy in women with essential thrombocytemia. Patients and methods: We conducted a retrospective study including all the pregnant women with essential thrombocytemia followed between January 2000 and January 2008 in a University Hospital (hôpital Jeanne-de-Flandre, Lille, France). We report our experience of 18 pregnancies in 13 women. The management and the complications of these pregnancies were reported. Results: All the patients were treated with low dose aspirin during the pregnancy. We observed one intrauterine death, one premature delivery at 29 weeks of gestation and six maternal haemorrhages at delivery (33%). Discussion and conclusion: It is essential to treat these patients with low dose aspirin as soon as the pregnancy begins. Aspirin will be continued in postpartum with anticoagulant treatment. This management appears to improve the obstetric outcome and decrease the thrombotic complications usually described. A national register seems to be necessary to evaluate the complications occurring during pregnancy and the optimum follow-up. [Copyright &y& Elsevier]

The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5 × 109/L at diagnosis (baseline analysis) was associated with thrombosis during the follow-up (Hazard Ratio [HR] of 1.8, p 0.03). At the time-dependent analysis, therapy with hydroxyurea (HU), lowering by 35% the baseline WBC level, reduced such strength of association giving a HR of 1.3 ( p value non significant). We found a trend between WBC level and thrombosis in untreated low-risk patients (RR of 1.9, 95% CI 0.9 to 3.1); in high-risk patients treated with HU this correlation was clearly lost (RR 1.1, 95% CI 0.2 to 2.7). Finally, we could not identify the presence of JAK2 V617F as a risk factor for thrombosis. Properly designed prospective studies should corroborate such results. [ABSTRACT FROM AUTHOR]

Background: The existence of a relationship between essential thrombocytemia (ET) and acute coronary syndromes (ACS) has been suggested. Method: Data from eleven consecutive patients admitted with ET in the cardiology department were reviewed. Results: Nine patients (82%) presented with ACS and two with bradycardia. Patients with ACS had a mean age of 67±11 years. Risk factors, especially hypertension (6, 66.7%), and smoking (6, 66.7%) were frequent. Average platelet count was 509 778±282 126/mm3. Significant coronary lesions were found in five of six patients studied with coronary angiography. During hospitalization, a patient suffered a thrombotic stroke, a massive pulmonary embolism, and partial aortic thrombosis. Another patient had a transient ischemic attack. Discharge treatments were aspirin (78%), clopidogrel (56%), acenocumarol (33%), hydroxyurea (56%) and anagrelide (44%). Three patients (27%) had thromboembolic events during follow-up (median 1.6 years), 2 patients had coronary events and 1 patient had venous thrombosis. There were neither significant haemorrhages nor deaths. Conclusions: Patients with ET and ACS have similar profiles to those of traditional ACS with frequent risk factors and significant coronary artery disease. Association with other thrombotic events can be seen during admission and follow-up while haemorrhagic complications seem to be rare. [ABSTRACT FROM AUTHOR]

Copyright of Italian Journal of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report two cases of foot ischemia combining microvascular thrombosis related to essential thrombocytemia (ET) and a proximal ulcerating atherosclerotic plaque. This suggests that myeloproliferative neoplasms could also trigger distal embolism from an unstable atherosclerotic plaque by creating a prothrombotic status. These distal ischemic events were the first ET manifestation and therefore lead to myeloproliferative neoplasm diagnosis. In ET, thrombosis event can occur with a normal platelet count. Furthermore, hemogram should be regularly controlled among JAK2 muted patients considering the frequent evolution from isolated JAK2 mutation to ET., (Copyright © 2021. Published by Elsevier Masson SAS.)

We present the case is presented of an acute coronary syndrome in a 30-year-old patient with essential thrombocythaemia. Acute coronary syndromes occur in 9% of cases in these patients, and their management constitutes a challenge for the cardiologist, specifically in terms of choosing the most appropriate antiplatelet therapy and its duration, taking into account that these patients have a high thrombotic risk, as well as a considerable haemorrhagic risk., (Copyright © 2019 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)