Clinical course and outcome of essential thrombocythemia and prefibrotic myelofibrosis according to the revised WHO 2016 diagnostic criteria

The recently revised World Health Organization (WHO) classification of myeloid neoplasms recognizes prefibrotic myelofibrosis (prePMF) as a distinct entity, characterized by well-defined histopathologic features together with minor clinical criteria (leukocytes, anemia, increased LDH, splenomegaly). The aim of the study was to examine the clinical relevance of distinguishing prePMF from essential thrombocythemia (ET). We identified in our database all patients affected with ET, prePMF and primary myelofibrosis (PMF) diagnosed according to 2008 WHO criteria with a bone marrow fibrosis grade 0-1 at diagnosis and one DNA sample to define the mutational status. The bone marrow morphology of all 404 identified patients was reviewed by an expert pathologist and patients were reclassified according to the 2016 WHO criteria. After reclassification, our cohort included 269 ET, 109 prePMF, and 26 myeloproliferative neoplasm unclassificable. In comparison with ET, patients with prePMF had higher leukocyte count, lower hemoglobin level, higher platelet count, higher LDH values, and higher number of circulating CD34-positive cells; they showed more frequently splenomegaly (all P values < ·001). CALR mutations were more frequent in prePMF than in ET (35·8% vs 17·8%, P < ·001). PrePMF patients had shorter overall survival (P < ·001) and a trend to a higher incidence of leukemic evolution (P ·067) compared to ET patients, while they did not differ in terms of thrombotic and bleeding complications. In conclusion, ET and prePMF diagnosed according to 2016 WHO criteria are two entities with a different clinical phenotype at diagnosis and a different clinical outcome.