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 Mesa; Jean-Jacques Kiladjian; Rȕdiger Hehlmann; Andreas Reiter; Francisco Cervantes; Claire Harrison; Mary Frances Mc Mullin; Hans Carl Hasselbalch; Steffen Koschmieder; Monia Marchetti; Andrea Bacigalupo; Guido Finazzi; Nicolaus Kroeger; Martin Griesshammer; Gunnar Birgegard; Giovanni Barosi

doi:10.1038/s41375-018-0077-1

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 Mesa, Jean-Jacques Kiladjian, Rȕdiger Hehlmann, Andreas Reiter, Francisco Cervantes, Claire Harrison, Mary Frances Mc Mullin, Hans Carl Hasselbalch, Steffen Koschmieder, Monia Marchetti, Andrea Bacigalupo, Guido Finazzi, Nicolaus KroegerMartin Griesshammer, Gunnar Birgegard, Giovanni Barosi

Department of Clinical Medicine

190 Citations (Scopus)

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.

Original language	English
Journal	Leukemia
Volume	32
Issue number	5
Pages (from-to)	1057-1069
ISSN	0887-6924
DOIs	https://doi.org/10.1038/s41375-018-0077-1
Publication status	Published - 1 May 2018

Keywords

Disease Management
Europe
Humans
Myeloproliferative Disorders/complications
Neoplasms/diagnosis
Philadelphia Chromosome
Pyrazoles/therapeutic use
Randomized Controlled Trials as Topic
Splenomegaly/drug therapy
Stem Cell Transplantation/methods

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Barbui, T., Tefferi, A., Vannucchi, A. M., Passamonti, F., Silver, R. T., Hoffman, R., Verstovsek, S., Mesa, R., Kiladjian, J.-J., Hehlmann, R., Reiter, A., Cervantes, F., Harrison, C., Mc Mullin, M. F., Hasselbalch, H. C., Koschmieder, S., Marchetti, M., Bacigalupo, A., Finazzi, G., ... Barosi, G. (2018). Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet. Leukemia, 32(5), 1057-1069. https://doi.org/10.1038/s41375-018-0077-1

Barbui, T, Tefferi, A, Vannucchi, AM, Passamonti, F, Silver, RT, Hoffman, R, Verstovsek, S, Mesa, R, Kiladjian, J-J, Hehlmann, R, Reiter, A, Cervantes, F, Harrison, C, Mc Mullin, MF, Hasselbalch, HC, Koschmieder, S, Marchetti, M, Bacigalupo, A, Finazzi, G, Kroeger, N, Griesshammer, M, Birgegard, G & Barosi, G 2018, 'Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet', Leukemia, vol. 32, no. 5, pp. 1057-1069. https://doi.org/10.1038/s41375-018-0077-1

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title = "Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet",

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.",

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author = "Tiziano Barbui and Ayalew Tefferi and Vannucchi, {Alessandro M} and Francesco Passamonti and Silver, {Richard T} and Ronald Hoffman and Srdan Verstovsek and Ruben Mesa and Jean-Jacques Kiladjian and Rȕdiger Hehlmann and Andreas Reiter and Francisco Cervantes and Claire Harrison and {Mc Mullin}, {Mary Frances} and Hasselbalch, {Hans Carl} and Steffen Koschmieder and Monia Marchetti and Andrea Bacigalupo and Guido Finazzi and Nicolaus Kroeger and Martin Griesshammer and Gunnar Birgegard and Giovanni Barosi",

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AU - Barbui, Tiziano

AU - Tefferi, Ayalew

AU - Vannucchi, Alessandro M

AU - Passamonti, Francesco

AU - Silver, Richard T

AU - Hoffman, Ronald

AU - Verstovsek, Srdan

AU - Mesa, Ruben

AU - Kiladjian, Jean-Jacques

AU - Hehlmann, Rȕdiger

AU - Reiter, Andreas

AU - Cervantes, Francisco

AU - Harrison, Claire

AU - Mc Mullin, Mary Frances

AU - Hasselbalch, Hans Carl

AU - Koschmieder, Steffen

AU - Marchetti, Monia

AU - Bacigalupo, Andrea

AU - Finazzi, Guido

AU - Kroeger, Nicolaus

AU - Griesshammer, Martin

AU - Birgegard, Gunnar

AU - Barosi, Giovanni

PY - 2018/5/1

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N2 - 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.

AB - 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.

KW - Disease Management

KW - Europe

KW - Humans

KW - Myeloproliferative Disorders/complications

KW - Neoplasms/diagnosis

KW - Philadelphia Chromosome

KW - Pyrazoles/therapeutic use

KW - Randomized Controlled Trials as Topic

KW - Splenomegaly/drug therapy

KW - Stem Cell Transplantation/methods

U2 - 10.1038/s41375-018-0077-1

DO - 10.1038/s41375-018-0077-1

M3 - Review

C2 - 29515238

SN - 0887-6924

VL - 32

SP - 1057

EP - 1069

JO - Leukemia

JF - Leukemia

IS - 5

ER -

Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet

Abstract

Keywords

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