Clinical Features, Gene Alterations, and Outcomes in Prefibrotic and Overt Primary and Secondary Myelofibrotic Patients.

Abstract

Simple SummaryThe final stages of myeloproliferative neoplasms (MPNs) are related to myelofibrosis (MF). This study aimed to compare secondary myelofibrosis (SMF), overt (PMF), and prefibrotic primary myelofibrosis (pre-PMF) and determine prognostic factors in clinical and genetic features. This study included 229 patients; 67 (29%), 122 (53%), and 40 (18%) cases were confirmed as SMF, overt PMF, and pre-PMF, respectively. We compare MFs, including pre-PMF, using six scoring stratifications associated with PMF and one scoring system with SMF. We also evaluated the impact of the genetic groups with clustering methods and previously reported genomic groups. We determined the clinical and genetic features associated with disease progression in SMF, overt PMF, and pre-PMF groups.The Philadelphia-negative myeloproliferative neoplasms (MPNs) are divided in three major groups: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 WHO classification incorporates also prefibrotic PMF (pre-PMF) and overt PMF. This study aimed to discriminate the clinical features, genetic alterations, and outcomes in patients with prefibrotic, overt PMF, and secondary MF (SMF). This study included 229 patients with diagnosed myelofibrosis (MF). Among 229 patients, 67 (29%), 122 (53%), and 40 (18%) were confirmed as SMF, overt PMF, and pre-PMF, respectively. The JAK2 V617F mutation was differentially distributed in SMF and PMF, contradictory to CALR and MPL mutations. Regarding nondriver mutations, the occurrence of ASXL1 mutations differed between PMF and SMF or pre-PMF. The three-year overall survival was 91.5%, 85.3%, and 94.8% in SMF, overt PMF, and pre-PMF groups. Various scoring systems could discriminate the overall survival in PMF but not in SMF and pre-PMF. Still, clinical features including anemia and thrombocytopenia were poor prognostic factors throughout the myelofibrosis, whereas mutations contributed differently. Molecular grouping by wild-type SF3B1 and SRSF2/RUNX1/U2AF1/ASXL1/TP53 mutations showed inferior progression-free survival (PFS) in PMF, SMF, and pre-PMF. We determined the clinical and genetic features related to poor prognosis in myelofibrosis.