Diagnosis and Management of Prefibrotic Primary Myelofibrosis (Pre-PMF)

This review is focused on prefibrotic primary myelofibrosis (pre-PMF) and evaluates clinical impact in relation to World Health Organization-defined essential thrombocythemia (ET). Compared to ET, patients with pre-PMF present with higher leukocyte counts, lower hemoglobin levels, higher lactate dehydrogenase values, and more frequently palpable splenomegaly. Incidences of JAK2V617F and CALR-mutated pre-PMF patients are superimposable to ET. Nondriver high-risk mutations in ASXL1, EZH2, SRSF2, and IDH 1/2 are increased in pre-PMF compared to ET. Vascular complications are not significantly different while hemorrhagic events are increased in pre-PMF. Median survival (around 13 vs. 19 years), 10-year cumulative rates progression to overt myelofibrosis, and transformation to blast phase are significantly different for pre-PMF versus ET. Primary objective of therapy is to prevent major thrombohemorrhagic complications. Because most pre-PMF patients fall in the lower prognostic IPSS group, observation alone or aspirin is recommended, while patients at intermediate risk may require a symptom-driven treatment and high-risk patients need cytostatic drugs.