Historical Views, Conventional Approaches, and Evolving Management Strategies for Myeloproliferative Neoplasms

Abstract

The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which include essential thrombocythemia, polycythemia vera, and myelofibrosis (MF), are in a new era of molecular diagnosis, ushered in by the identification of the JAK2(V617F) and cMPL mutations in 2005 and 2006, respectively, and the CALR mutations in 2013. Coupled with increased knowledge of disease pathogenesis and refined diagnostic criteria and prognostic scoring systems, a more nuanced appreciation has emerged of the burden of MPN in the United States, including the prevalence, symptom burden, and impact on quality of life. Biological advances in MPN have translated into the rapid development of novel therapeutics, culminating in the approval of the first treatment for MF, the JAK1/JAK2 inhibitor ruxolitinib. However, certain practical aspects of care, such as those regarding diagnosis, prevention of vascular events, choice of cytoreductive agent, and planning for therapies, present challenges for hematologists/oncologists, and are discussed in this article.

The evolution and clinical relevance of prognostic classification systems in myelofibrosis

“…Myelofibrosis (MF), whether arising de novo (primary myelofibrosis [PMF]) or from essential thrombocythemia (ET) or polycythemia vera (PV), is a clonal Philadelphia chromosome‐negative (Ph‐) myeloproliferative neoplasm (MPN) characterized by anemia, hepatosplenomegaly, extramedullary hematopoiesis, constitutional symptoms, an increased risk of leukemic transformation (LT), and shortened survival . In 2010, there were an estimated 13,000 individuals with MF living in the United States, for a prevalence of approximately 4 to 6 cases per 100,000 population . The symptom burden of MF is significant, and can be attributed to cytokine excess, splenomegaly, thrombotic complications, and cytopenias .…”

New Strategies in Myeloproliferative Neoplasms: The Evolving Genetic and Therapeutic Landscape

“…Of these original MPNs, CML was separated with the discovery of the Philadelphia chromosome, while the term “classical MPN” came to be used for PV, ET and MF. In 2010, the prevalence of ET, PV and MF was 134,000, 148,000 and 13,000, respectively, in the United States(2). PV and MF are more common in males, while there is a small preponderance for females in ET(3).…”

“…There is controversy over the leukemogenicity of single-agent HU, although multiple studies suggest this concern is unsubstantiated(50–52). The ANAHYDRET study demonstrated noninferiority of anagrelide to HU in lowering thrombotic risk in WHO-classified high-risk ET, but the larger UK-PT1 trial found anagrelide is more often associated with arterial thrombosis, hemorrhage and myelofibrotic transformation (2, 6, 53, 54). …”

NCCN Guidelines Insights: Myeloproliferative Neoplasms, Version 2.2018

“…3,4 However, certain aspects of clinical management regarding the diagnosis, assessment of symptom burden, and selection of appropriate symptom-directed therapies continue to present challenges for hematologists and oncologists. 5 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPNs provide recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for disease management in adults. These NCCN Guide-NCCN Guidelines Insights CE lines Insights discuss the recommendations outlined in the NCCN Guidelines for the risk stratification, treatment, and special considerations for the management of PV and ET.…”