Prefibrotic Myelofibrosis (PreMF) Belongs to a Continuum of Epidemiological, Clinical and Histological Characteristics Featuring Primary Myelofibrosis (PMF)

Abstract 1743 Background: WHO diagnostic criteria of myeloproliferative neoplasms (MPNs) identify a preMF variant including patients having absence or early grade fibrosis, dual myeloid and megakaryocytic dominance, and clusters of atypical, ectopic, variable in size megakaryocytes in the bone marrow (BM). Many issues on the variant are critical, such as its distinction from essential thrombocythemia, recognisability, biological identity and true place among MPNs. Here we describe the clinical presentation of patients with preMF collected among a large cohort of patients diagnosed with PMF according WHO and for whom long-term follow-up data were available. The aim is to investigate whether there is an underlying structure of the patients' characteristics that allows to assign them to a distinct variant of MPNs or to align them along a continuum in the realm of PMF. Methods: We included in this study patients with PMF who were referred to the Center for the Study of Myelofibrosis of IRCCS Policlinico S. Matteo Foundation, Italy from 1990 to 2011. In all patients the BM biopsy taken at diagnosis was reviewed (pathologist: UM) and the diagnosis of preMF was established adopting the stringent criterion that, besides typical BM cellularity and megakaryocyte morphology, BM had less than grade 1 reticulin fibrosis (EUMNET criteria). Results: Of the 659 patients with PMF, 126 fulfilled the criteria we established for the diagnosis of preMF, thus accounting for 19.1% of the cohort. Female sex accounted for 59.5% of the preMF cohort while it accounted for 33.8% of PMF fibrotic type (P In order to assign patients with PMF to groups with different degrees of BM fibrosis, we further categorized MF fibrotic type into early MF (BM fibrosis grade 1) and advanced MF (BM fibrosis grade 2 or 3). Female frequency steadily varied from 59.5% to 43.2% and 25.6% in the 3 categories of BM fibrosis, respectively. Age varied from 39.2, 50.4, 57.0 years, respectively. Hemoglobin and platelet count steadily decreased (Hb=14.0, 13.3, 11.2 g/dL, respectively; platelet count=647, 554, 346 x109/L, respectively). Spleen size steadily increased along with increasing of BM fibrosis (spleen index=120, 152, 200). All these parameters exhibited a statistically significant trend along the continuum of BM fibrosis grade (ANOVA, P Conclusions: The BM picture of preMF identifies a group of patients with PMF associated with a very indolent hematologic phenotype, female dominance and very young age at presentation characterized by high incidence of splanchnic vein thrombosis. Disclosures: Barosi: Novartis: Membership on an entity's Board of Directors or advisory committees.