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.
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AMV, FP, and G Ba were supported by a grant from Associazione Italiana per la Ricerca sul Cancro (AIRC; Milan, Italy), Special Program Molecular Clinical Oncology 5 × 1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project #1005.
TB, AT, and GBa developed the study design. GBa did the critical appraisal of evidence of the randomized trials. TB and AT wrote the first draft of the recommendations. All the authors participated to the consensus meetings. GBa wrote the manuscript. All authors critically revised, reviewed, and approved the final version of this study.
Conflict of interest
TB received advisory board fee from Novartis; FC received advisory board fee from Novartis, honoraria from Novartis, AOP Orphan Disease and Shire, and speaker bureau fee from Novartis, AOP and Shire; AMV received advisory board fee from Novartis, and Speaker bureau fee from Novartis and Shire; MM received speaker bureau fee from Gilead and Amgen; SK received research funding from Novartis, Bristol-Myers Squibb, and Janssen, honoraria and advisory board fees from Novartis, Incyte/Ariad, Pfizer, Bristol-Myers Squibb, Janssen, AOP, CTI, and travel support from Shire; AR received advisory board fee and honoraria from Novartis; MG received honoraria from Shire, Novartis, Baxalta, AOP Orphan Disease, Gilead and Janssen; JJK received advisory board fee and funding from Novartis and AOP Orphan; AB received honoraria form Novartis, Therakos, Sanofi and Adienne, and advisory board fee from Novartis; MFMM received honoraria and consulting fee from Novartis and Gilead; SV received support for research from: Incyte Corporation, Roche, Astra Zeneca, Lilly Oncology, NS Pharma, Bristol Mayers Squibb, Celgene, Gilead, Seattle Genetics, Promedior, CTI BioPharma Corp., Galena BioPharma, Pfizer, Genentech, Blueprint Medicines Corp.; RM received consulting fee from Novartis, AOP, Shire, and research funding from Incyte, Gilead, Pharmessential, Celgene and Promedior; R Ho received research funding from Incyte and Janssen; FP served on advisory boards for Sanofi, Gilead, Janssen Pharmaceutical, Celgene, Novartis, Bristol-Myers Squibb and Roche; GB received advisory board fee from Novartis. GF and G Bi have no conflict of interest.
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Barbui, T., Tefferi, A., Vannucchi, A.M. et al. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia 32, 1057–1069 (2018). https://doi.org/10.1038/s41375-018-0077-1
Combination therapy with interferon and ruxolitinib for polycythemia vera and myelofibrosis: are two drugs better than one?
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