Philadelphia chromosome-negative classical myeloproliferative neoplasms: Revised management recommendations from European LeukemiaNet
Tiziano Barbui,Ayalew Tefferi,Alessandro M. Vannucchi,Francesco Passamonti,Richard T. Silver,Ronald Hoffman,Srdan Verstovsek,Ruben A. Mesa,Jean-Jacques Kiladjian,Rèdiger Hehlmann,Andreas Reiter,Francisco Cervantes,Claire N. Harrison,Mary F. Mc Mullin,Hans Carl Hasselbalch,Steffen Koschmieder,Monia Marchetti,Andrea Bacigalupo,Guido Finazzi,Nicolaus Kroeger,Martin Griesshammer,Gunnar Birgegård,Giovanni Barosi +22 more
TLDR
This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs), and both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea.Abstract:
This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.read more
Citations
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Life after ruxolitinib: Reasons for discontinuation, impact of disease phase, and outcomes in 218 patients with myelofibrosis
Francesca Palandri,Massimo Breccia,Massimiliano Bonifacio,Nicola Polverelli,Elena Maria Elli,Giulia Benevolo,Mario Tiribelli,Elisabetta Abruzzese,Alessandra Iurlo,Florian H. Heidel,Micaela Bergamaschi,Alessia Tieghi,Monica Crugnola,Francesco Cavazzini,Gianni Binotto,Alessandro Isidori,Nicola Sgherza,Costanza Bosi,Bruno Martino,Roberto Latagliata,Giuseppe Auteri,Luigi Scaffidi,Davide Griguolo,Malgorzata Monika Trawinska,Daniele Cattaneo,Lucia Catani,Mauro Krampera,Roberto M. Lemoli,Antonio Cuneo,Gianpietro Semenzato,Robin Foà,Francesco Di Raimondo,Daniela Bartoletti,Michele Cavo,Giuseppe A. Palumbo,Nicola Vianelli +35 more
TL;DR: After discontinuing ruxolitinib, the outcome of patients with myelofibrosis reportedly has been poor and reasons for drug discontinuation, disease phase at discontinued drug, and salvage therapies may influence the outcome.
Journal ArticleDOI
Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study
Jean-Jacques Kiladjian,Pierre Zachee,Masayuki Hino,Fabrizio Pane,Tamás Masszi,Claire N. Harrison,Ruben A. Mesa,Carole B. Miller,Francesco Passamonti,Simon Durrant,Martin Griesshammer,Keita Kirito,Carlos Besses,Beatriz Moiraghi,Elisa Rumi,Vittorio Rosti,Igor Wolfgang Blau,Nathalie Francillard,Tuochuan Dong,Monika Wroclawska,Alessandro M. Vannucchi,Srdan Verstovsek +21 more
TL;DR: This study aimed to compare the long-term safety and efficacy of ruxolitinib with best available therapy in patients with polycythaemia vera who were resistant to or intolerant of hydroxyurea and assessed the durability of primary composite response, complete haematological remission, Overall survival, patient-reported outcomes, and safety after 5-years of follow-up.
Journal ArticleDOI
Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis
Alessandra Carobbio,Alberto Ferrari,Arianna Masciulli,Arianna Ghirardi,Giovanni Barosi,Tiziano Barbui +5 more
TL;DR: The pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis, and an investigation on individual patient data in a large collective archive of homogeneous patients is warranted.
Journal ArticleDOI
Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis.
TL;DR: Luspatercept (and sotatercept), ligand traps that particularly inhibit GDF11, lead to RBC transfusion independence in 10% to 50% of lower-risk MDSs resistant to available treatments, and have started to be used in PMF.
Journal ArticleDOI
High mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib.
Tiziano Barbui,Alessandro M. Vannucchi,Alberto Alvarez-Larrán,Alessandra Iurlo,Arianna Masciulli,Alessandra Carobbio,Arianna Ghirardi,Alberto Ferrari,Giuseppe Rossi,Elena Maria Elli,Marcio Andrade-Campos,Mercedes Gasior Kabat,Jean-Jaques Kiladjian,Francesca Palandri,Giulia Benevolo,Valentín García-Gutiérrez,Maria Laura Fox,Maria Angeles Foncillas,Carmen Montoya Morcillo,Elisa Rumi,Santiago Osorio,Petros Papadopoulos,Massimiliano Bonifacio,Keina Susana Quiroz Cervantes,Miguel Sagues Serrano,Gonzalo Carreño-Tarragona,Marta Sobas,Francesca Lunghi,Andrea Patriarca,Begona Navas Elorza,Anna Angona,Elena Magro Mazo,Steffen Koschmieder,Marco Ruggeri,Beatriz Cuevas,Juan Carlos Hernández-Boluda,Emma Lopez Abadia,Blanca Xicoy Cirici,Paola Guglielmelli,Marta Garrote,Daniele Cattaneo,Rosa Daffini,Fabrizio Cavalca,Beatriz Bellosillo,Lina Benajiba,Natalia Curto-Garcia,Marta Bellini,Silvia Betti,Valerio De Stefano,Claire N. Harrison,Alessandro Rambaldi +50 more
TL;DR: In this article, the clinical presentation and risk factors for survival in 175 patients with myeloproliferative neoplasms (MPN) and COVID-19, diagnosed between February and June 2020, were reported.
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