Philadelphia-Negative Classical Myeloproliferative Neoplasms: Critical Concepts and Management Recommendations From European LeukemiaNet

Unit of Clinical Epidemiology/Center for the Study of Myelofibrosis, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Viale Golgi 19, 27100 Pavia, Italy.
Journal of Clinical Oncology (Impact Factor: 18.43). 02/2011; 29(6):761-70. DOI: 10.1200/JCO.2010.31.8436
Source: PubMed


We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

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    • "Based on European Leukaemia Net recommendations (Barbui et al, 2011), in the absence of sufficient data to recommend any treatment, paediatricians individually tailored the treatment to each patient. "
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    ABSTRACT: Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment. © 2015 John Wiley & Sons Ltd.
    Full-text · Article · Feb 2015 · British Journal of Haematology
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    • "A young, asymptomatic patient with a platelet count of less than 1500 × 10 9 /L should be considered at a low risk of thrombosis and hemorrhagic events, and does not need cytoreductive drugs, only ASA [12] [21]. By contrast, advanced age of 60 years or more, a history of serious bleeding or thrombosis, or a platelet level over 1500 × 10 9 /L, are indications for cytoreductive drugs [21]. The myelosuppressive agent of choice in patients who suffer from ET and have risk of vascular thrombosis or bleeding is HU [19]. "
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    ABSTRACT: Essential thrombocythemia (ET), a chronic myeloproliferative disease, is characterized by an increased number of platelets and risk of vascular thrombosis. A case of a patient treated for ET who had acute myocardial infarction (MI) and reinfarction within a month is presented. A 55-year-old male patient was hospitalized because of subacute inferolateral non-ST-segment-elevation MI, without risk factors for cardiovascular diseases. The patient has been treated for ET for the past 8 years, received anagrelide for the past two years. The first coronary-angiography did not detect significant stenosis of epicardial vessels; the patient was discharged in stable condition with anagrelide therapy. Two weeks later, the patient had an acute anterolateral ST-segment-elevation MI. Primary percutaneous coronary intervention showed thrombus in the distal part of the left anterior descending coronary artery. Percutaneous transluminal coronary angioplasty was performed and eptifibatide was administered after the procedure. There was no residual stenosis, prescribed therapy included clopidogrel and low-molecular-weight heparin. Anagrelide therapy was replaced with hydroxyurea (HU) and acetylsalicylic acid (ASA). It is necessary to treat ET in line with the standard treatment protocol for coronary diseases. In the treatment of high-risk hematology patients anagrelide proved to be a worse option than the combination of HU and ASA.
    Full-text · Article · Nov 2013 · Journal of Cardiology Cases
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    • "There was no particular exclusion criterion. Peg-IFNa-2a was prescribed off-label in accordance with local practice and following French and International recommendations (Barbui et al, 2011). The study was approved by the FIM institutional review board. "
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    ABSTRACT: Myeloproliferative neoplasm-related myelofibrosis is associated with cytopenic or proliferative phases, splenomegaly and constitutional symptoms. Few effective treatments are available and small series suggested that interferon could be an option for myelofibrosis therapy. We performed a retrospective study of pegylated-interferon α-2a (Peg-IFNα-2a) therapy in myelofibrosis. Sixty-two patients treated with Peg-IFNα-2a at 17 French and Belgian centres were included. Responses were determined based on the criteria established by the International Working Group for Myelofibrosis Research and Treatment. Mean follow-up was 26 months. Sixteen of 25 anaemic patients (64%) (eight concomitantly receiving recombinant erythropoietin) achieved a complete response and transfusion-independence was obtained in 5/13 patients (38·5%). Constitutional symptoms resolved in 82% of patients. All five leucopenic patients normalized their leucocyte counts, whereas a normal platelet count was obtained in 5/8 thrombocytopenic patients. Splenomegaly was reduced in 46·5% of patients, and complete resolution of thrombocytosis and leucocytosis were observed in 82·8% and 68·8% of patients, respectively. Side effects (mostly haematological) were mainly of grade 1-2. The only factor independently associated with treatment failure was a spleen enlargement of more than 6 cm below the costal margin. In conclusion, Peg-IFNα-2a induced high response rates with acceptable toxicity in a large proportion of patients with primary and secondary myelofibrosis, especially in early phases.
    Full-text · Article · Jul 2013 · British Journal of Haematology
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