Myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are clonal disorders of the myeloid lineage that clinically present as an excess of cells from one or more terminally differentiated myeloid compartments (Figure 76.1). Although there are a spectrum of MPNs involving all of the different myeloid compartments, the most common MPN are polcythemia vera (PV), essential thrombocytosis (ET), primary myelofibrosis (PMF), and chronic myeloid leukemia (CML). CML is characterized by neutrophilia and by the invariant presence of the BCR–ABL fusion tyrosine kinase, and is the subject of detailed discussion elsewhere in this volume. PV clinically presents with increased red blood-cell counts (hemoglobin and hematocrit), with variable involvement of the platelet and white blood-cell lineages. In contrast, patients with ET present with thrombocytosis without increased erythrocytosis. PMF is associated with a leukoerythroblastosis, splenomegaly, extra-medullary hematopoiesis, and systemic symptoms, and on bone-marrow exam PMF patients are found to have reticulin fibrosis. Over time, a subset of PV and ET patients progress myelofibrosis (MF); post-PV/ET MF is not distinguishable clinically or biologically from de novo PMF.

A significant proportion of MPN patients are diagnosed based on the identification of asymptomatic abnormalities on a complete blood count. A subset of patients at diagnosis, or with disease progression, develop symptomatic splenomegaly, constitutional symptoms, thrombosis, bleeding, or infection. From a clinical perspective, the most feared complications to occur over time are progressive bone-marrow failure or transformation to acute myeloid leukemia (AML), which are associated with an adverse overall prognosis (1). Therefore the current goals in MPN treatment are to ameliorate symptoms, and to prevent disease progression and transformation.