The European LeukemiaNet Consortium recently updated its guidelines for treating Philadelphia chromosome-negative myeloproliferative neoplasms for the first time since 2011. These classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (EV) and primary myelofibrosis (MF).

The revised guidelines, published in Leukemia, reflect the greater understanding of these diseases gained during the last decade as researchers have identified key mutations and the pathophysiology of myeloid proliferation. In addition, the guidelines provide guidance on treatment selection and sequencing.

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In recognition of changes to the World Health Organization’s (WHO) definition of polycythemia vera, the guidelines reduced the threshold values for hemoglobin/hematocrit to 16.5 g/dl/49% for men and 16 g/dl/48% in women. The revised criteria also emphasized the need for bone marrow examination for definitive diagnosis and expert histology to ensure proper classification of the neoplasm.

The key mutations in MPNs include JAK2V617, CALR or MPL. The guidelines now also recommend that clinicians search for complementary clonal markers—ASXL1, EZH2, IDH1/IDH2, and SRSF2—in patients who test negative for the common MPN-associated driver mutations but in whom these neoplasms are suspected.

The update included a number of changes in therapy recommendations, with ruxolitinib assuming prominence. Both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are now recommended as second-line therapies for polycythemia vera patients who cannot tolerate or have inadequate response to hydroxyurea. Ruxolitinib is also recommended in the first-line for patients with MF-associated splenomegaly who have intermediate-2 or high-risk disease and for patients who have intermediate-1 disease with highly symptomatic splenomegaly.

The guidelines recommend allogeneic stem cell transplantation for transplant-eligible myelofibrosis patients with high or intermediate-2 risk score and for high risk patients with intermediate-1 risk score. Risk factors include refractory, transfusion-dependent anemia, more than 2% blasts in peripheral blood, adverse cytogenetics or high-risk mutations.