Overview of Myelofibrosis Types and Presentations
Aaron Gerds, MD, MS, explains the types, presentations, and classic symptoms of myelofibrosis.
Transcript:
Aaron Gerds, MD, MS: My name is Aaron Gerds, and I’m an associate professor of medicine here at the Cleveland Clinic Taussig Cancer Institute [Cleveland, OH]. I also serve as the medical director for the clinical research office at the Case Comprehensive Cancer Center [Cleveland, OH], and the deputy director for clinical research at the Taussig Cancer Institute.
The typical patient with myelofibrosis is a patient who has abnormal blood counts and often has constitutional symptoms. We think about weight loss, night sweats, fevers, itchy skin, as well as spleen-related symptoms such as early satiety and abdominal discomfort. That’s coupled again with blood count changes—elevated white blood cell count, anemia, and thrombocytopenia. That constellation of things makes you think about myelofibrosis.
In terms of developing myelofibrosis, there are some things that can increase your risk, such as having a preexisting MPN [myeloproliferative neoplasm], such as PV [polycythemia vera] or ET [essential thrombocythemia]. Some studies link benzene exposure, smoking exposure, and ionizing radiation exposure to developing MPNs. Environmental factors are largely undescribed. Lastly, there are some familial cases of MPN where people inherit a predisposition for developing MPNs. We look to some families where there’s a person who has an MPN and then their sibling has an MPN and maybe a parent might have had MPN and we really try to learn more from those cases about the biologic origins of these diseases.
In general, myelofibrosis has 3 domains of things that are deranged. We think about blood counts being abnormal. We think about symptoms that are present as well as an enlarged spleen. If you kind of break it down into those 3 categories, the constellation of things that occur with myelofibrosis is pretty straightforward. With the blood counts, patients have leukocytosis. They have leukoerythroblastosis as well as anemia and thrombocytopenia. That can lead to symptoms of feeling fatigued or worn down and an increased risk of bleeding.
Within the constitutional symptoms, we think about night sweats, fevers, and itchy skin often as your classic cytokine-driven symptoms. Then, lastly, the splenomegaly. The spleen enlarges due to the elevated cytokine levels and to some degree extramedullary hematopoiesis. That can lead to symptoms like early satiety and abdominal discomfort as well as weight loss. Therapies that we use in myelofibrosis target each of these domains of presentation, whether we’re discussing abnormal blood counts, constitutional symptoms, or spleen-related symptoms.
There are different types of myelofibrosis. This is not a monolith of disease. Some patients present with very proliferative disease where their white count is high and maybe even their platelets or red cells are high. They have all the criteria met for making the diagnosis. Other patients who present with very empty marrows, marrows that look like deserts, and they all often have low blood counts. The more we’ve looked into these different ends of the spectrum, the more we learn about the pathobiology of the disease is different. For example, patients with more proliferative myelofibrosis may have higher allele burdens of the driver mutations, whereas patients who have more cytopenic myelofibrosis or spent myelofibrosis or burned-out myelofibrosis may have lower allele burdens of the driver mutations and often second and third mutations that drive disease as well.
Often responsive therapy might be different. We think of certain JAK [Janus kinase] inhibitors working better in more proliferative myelofibrosis and other JAK inhibitors potentially working better in more cytopenic myelofibrosis. There’s clearly a distinction within this disease. Again, it is not a monolith, and we want to think about how to apply these different therapies that we now have in the appropriate populations.
Transcript edited for clarity.
