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.
    British Journal of Haematology 02/2015; 169(4). DOI:10.1111/bjh.13329 · 4.71 Impact Factor
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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.
    British Journal of Haematology 07/2013; 162(6). DOI:10.1111/bjh.12459 · 4.71 Impact Factor
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    • "Until recently, allogeneic haematopoietic stem cell transplantation has been the only potentially curative treatment for patients with MF, but an option that was traditionally only feasible for a small percentage of patients, namely the younger and physically fit. However, recent studies suggest that it may be utilised in older individuals as well (14,15). Other therapeutic modalities (e.g., thalidomide, hydroxyurea, corticosteroids, anagrelide, androgens, splenectomy or spleen irradiation, transfusions, pirfenidone and suramin) are only palliative and do not provide a substantial improvement in survival rates (16–32). "
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    ABSTRACT: The aim of the present study was to assess the beneficial and harmful effects of ruxolitinib in patients with myelofibrosis (MF). The Cochrane databases, PubMed and Embase were searched for studies published up to October 2012. Randomised controlled trials assessing ruxolitinib versus a placebo or the best available therapy in patients with MF were included. Two trials randomised 528 patients with MF to ruxolitinib versus a placebo or ruxolitinib versus the best available therapy. Compared with the placebo, ruxolitinib had a significant beneficial effect on the proportion of patients that had a reduction in spleen volume of ≥35% at 24 weeks [odds ratio (OR), 109.78; 95% confidence interval (CI), 14.97-804.78] or an increased overall survival rate (OR, 2.02; 95% CI, 0.99-4.12). Ruxolitinib significantly increased the risk of several non-haematological or haematological adverse events, but not the risk of treatment discontinuations (OR, 1.04; 95% CI, 0.50-2.14). Compared with the best available therapy, ruxolitinib had a significant beneficial effect on the proportion of patients that had a reduction in spleen volume of ≥35% at 24 (OR, 68.45; 95% CI, 4.15-1129.19) or 48 weeks (OR, 56.20; 95%CI, 3.40-928.67). Ruxolitinib once again significantly increased the risk of several non-haematological adverse events, serious adverse events and dose reductions or interruptions (OR, 9.60; 95% CI, 4.66-19.81), but not the risk of treatment discontinuations (OR, 1.54; 95% CI, 0.48-4.97). In conclusion, based on the trials included in the present study, the use of ruxolitinib is beneficial in the treatment of MF.
    Experimental and therapeutic medicine 03/2013; 5(3):927-931. DOI:10.3892/etm.2013.886 · 1.27 Impact Factor
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