An Overview of Myeloproliferative Neoplasms

Srdan Verstovsek, MD, PhD: Classic myeloproliferative neoplasms are polycythemia vera [PV], myelofibrosis, and essential thrombocythemia [ET]. Essential thrombocythemia is the easiest to understand; the bone marrow makes too many platelets. That’s where the name comes from. It is driven by the underlying biological problem, which is not only related to the essential thrombocythemia, but it’s also related to polycythemia vera and myelofibrosis. This is uncontrolled growth of the cells due to hyperactivity of the intracellular signaling of the JAK-STAT pathway.

In this regard, essential thrombocythemia is relatively benign, unlike myelofibrosis and polycythemia vera, which tells us that some other contributors exist that would explain aggressiveness of myelofibrosis, for example. But in ET, too many platelets predispose patients to blood clotting and does not affect their survival. The goal of therapy, therefore, is to decrease the risk of blood clotting by controlling that thrombotic number and to make sure that patients have good quality of life.

Polycythemia vera, as the name implies, is a disease of all the cells. Polycythemia means all the cells grow in the blood. Again, this is a disease of the bone marrow with the same biological problem as essential thrombocythemia but presenting differently. Too many red blood cells, that’s No. 1; 60% of patients have high white cells, and 60% have high platelets. Some may have a big spleen, or systemic symptoms from circulatory problems. Life expectancy is close to normal. And like in ET, thrombotic events are the main problem. We need to control the thrombotic risk, because the risk of dying is related to too many blood cells in circulation, and thrombosis can, unnecessarily I should say, shorten the life expectancy. Assessment of thrombotic risk, the same as in ET, is paramount.

In myelofibrosis, we are talking about something else. There is a growth of fibers in the bone marrow. We believe it’s possibly a reaction to the presence of malignancy. Some patients present early with the disease with not too much fiber, maybe no fibers at all; this is so-called prefibrotic myelofibrosis. These patients present like patients with essential thrombocythemia, with too many platelets, and we treat them as we do patients with ET, decreasing thrombotic risk. But the bulk of patients with myelofibrosis are the ones who come with fibers in the bone marrow that limit the growth of the cells. This results in anemia, thrombocytopenia, low white cell count, particularly anemia, very big spleen, big liver, bad quality of life, night sweating, low-grade fevers, itching, and a shorter life expectancy of 5 to 7 years.

You can say that ET and PV are relatively benign; thrombosis is a problem. Myelofibrosis has multiple other problems: low blood cell count, big organs, bad quality of life, and short life expectancy.

Transcript Edited for Clarity