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Prognostic scoring systems for primary myelofibrosis (PMF) are not accurate in patients with post-essential thrombocythemia and post-polycythemia vera myelofibrosis (PET-MF; PPV-MF). Given the paucity of data describing the clinical characteristics, disease course and outcomes of these patients, we sought to describe and compare the clinical characteristics and outcomes of 755 patients with PMF, 181 with PPV-MF, and 163 with PET-MF referred to our institution between 1984 and 2013. The median follow-up was 31 months, and 56% (n=616) patients had died. Over an observation period of 3502 person-years, 11% of patients had progression to AML, with similar rates among groups. The proportion of patients with transfusion dependency (higher in PMF), leukocytosis and systemic symptoms (higher in PPV-MF), and thrombocytopenia (higher in PMF, PPV-MF) differed among groups. Median overall survival (OS) was longest in PET-MF patients (73 mo vs 45 mo (PMF) vs 48 mo (PPV-MF), p <0.001). Stratification of OS by DIPSS was only discriminatory in patients with PMF, and it failed to distinguish higher risk patients with PPV/PET-MF. In multivariate analysis, predictors of inferior OS were higher age, anemia, systemic symptoms, thrombocytopenia, and high peripheral blasts in PMF; age, anemia, and systemic symptoms for PPV-MF; and anemia, peripheral blasts and thrombocytopenia in PET-MF. Although the clinical characteristics of PPV/PET-MF patients are not substantially different from those with PMF, their outcomes differ and prognostic scoring systems for PET/PPV-MF should be improved., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Despite significant improvements in the signs and symptoms of myelofibrosis (MF), and possible prolongation of patients' survival, some have disease that is refractory to ruxolitinib and many lose their response over time. Furthermore, patients with ≥3 mutations are less likely to respond to ruxolitinib. Here we describe outcomes after ruxolitinib discontinuation in MF patients enrolled in a phase 1/2 study at our center. After a median follow-up of 79 months, 86 patients had discontinued ruxolitinib (30 of whom died while on therapy). The median follow-up after ruxolitinib discontinuation for the remaining 56 patients was 32 months, with median survival after discontinuation of 14 months. Platelets <260 × 109/L at the start of therapy or <100 × 109/L at the time of discontinuation were associated with shorter survival after discontinuation. Of 62 patients with molecular data at baseline and follow-up, 22 (35%) acquired a new mutation while receiving ruxolitinib (14 [61%] in ASXL1). Patients showing clonal evolution had significantly shorter survival after discontinuation (6 vs 16 months). Transfusion dependency was the only clinical variable associated with clonal evolution. These findings underscore the need for novel therapies and suggest that clonal evolution or decreasing platelet counts while on ruxolitinib therapy may be markers of poor prognosis. [ABSTRACT FROM AUTHOR]

Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia ( p = 0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis. [ABSTRACT FROM AUTHOR]