TY - JOUR
T1 - Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis
AU - Guglielmelli, Paola
AU - Guglielmelli, Paola
AU - Pacilli, Annalisa
AU - Pacilli, Annalisa
AU - Rotunno, Giada
AU - Rotunno, Giada
AU - Rumi, Elisa
AU - Rumi, Elisa
AU - Rosti, Vittorio
AU - Delaini, Federica
AU - Maffioli, Margherita
AU - Maffioli, Margherita
AU - Fanelli, Tiziana
AU - Fanelli, Tiziana
AU - Fanelli, Tiziana
AU - Pancrazzi, Alessandro
AU - Pancrazzi, Alessandro
AU - Pietra, Daniela
AU - Salmoiraghi, Silvia
AU - Mannarelli, Carmela
AU - Mannarelli, Carmela
AU - Franci, Annalisa
AU - Franci, Annalisa
AU - Paoli, Chiara
AU - Paoli, Chiara
AU - Rambaldi, Alessandro
AU - Rambaldi, Alessandro
AU - Passamonti, Francesco
AU - Passamonti, Francesco
AU - Barosi, Giovanni
AU - Barbui, Tiziano
AU - Cazzola, Mario
AU - Cazzola, Mario
AU - Vannucchi, Alessandro M.
AU - Vannucchi, Alessandro M.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - The 2016 revision of the World Health Organization (WHO) classification of myeloproliferative neoplasms defines 2 stages of primary myelofibrosis (PMF): prefibrotic/early (pre-PMF) and overt fibrotic (overt PMF) phase. In this work, we studied the clinical and molecular features of patients belonging to these categories of PMF. The diagnosis of 661 PMF patients with a bone marrow biopsy at presentation was revised according to modern criteria; clinical information and annotation of somatic mutations in both driver and selected nondriver myeloid genes were available for all patients. Compared with pre-PMF, overt PMF was enriched in patients with anemia, thrombocytopenia, leukopenia, higher blastcount, symptoms, large splenomegaly, and unfavorable karyotype. The different types of driver mutations were similarly distributed between the 2 categories, whereas selected mutations comprising the high mutation risk (HMR) category (any mutations in ASXL1, SRSF2, IDH1/2, EZH2) were more represented in overt PMF. More patients with overt PMF were in higher International Prognostic Scoring System risk categories at diagnosis, and the frequency increased during follow-up, suggesting greater propensity to disease progression compared with pre-PMF. Median survival was significantly shortened in overt PMF (7.2 vs 17.6 years), with triple negativity for driver mutations and presence of HMR mutations representing independent predictors of unfavorable outcome. The findings of this "real-life" study indicate that adherence to 2016 WHO criteria allows for identification of 2 distinct categories of patients with PMF where increased grades of fibrosis are associated with more pronounced disease manifestations, adverse mutation profile, and worse outcome, overall suggesting they might represent a phenotypic continuum.
AB - The 2016 revision of the World Health Organization (WHO) classification of myeloproliferative neoplasms defines 2 stages of primary myelofibrosis (PMF): prefibrotic/early (pre-PMF) and overt fibrotic (overt PMF) phase. In this work, we studied the clinical and molecular features of patients belonging to these categories of PMF. The diagnosis of 661 PMF patients with a bone marrow biopsy at presentation was revised according to modern criteria; clinical information and annotation of somatic mutations in both driver and selected nondriver myeloid genes were available for all patients. Compared with pre-PMF, overt PMF was enriched in patients with anemia, thrombocytopenia, leukopenia, higher blastcount, symptoms, large splenomegaly, and unfavorable karyotype. The different types of driver mutations were similarly distributed between the 2 categories, whereas selected mutations comprising the high mutation risk (HMR) category (any mutations in ASXL1, SRSF2, IDH1/2, EZH2) were more represented in overt PMF. More patients with overt PMF were in higher International Prognostic Scoring System risk categories at diagnosis, and the frequency increased during follow-up, suggesting greater propensity to disease progression compared with pre-PMF. Median survival was significantly shortened in overt PMF (7.2 vs 17.6 years), with triple negativity for driver mutations and presence of HMR mutations representing independent predictors of unfavorable outcome. The findings of this "real-life" study indicate that adherence to 2016 WHO criteria allows for identification of 2 distinct categories of patients with PMF where increased grades of fibrosis are associated with more pronounced disease manifestations, adverse mutation profile, and worse outcome, overall suggesting they might represent a phenotypic continuum.
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U2 - 10.1182/blood-2017-01-761999
DO - 10.1182/blood-2017-01-761999
M3 - Article
C2 - 28351937
AN - SCOPUS:85021124577
VL - 129
SP - 3227
EP - 3236
JO - Blood
JF - Blood
SN - 0006-4971
IS - 24
ER -