Aaron Gerds, MD, explains the various types of myelofibrosis and the underlying pathophysiologies.
John Mascarenhas, MD: Aaron, are there different types of myelofibrosis? If so, how do you look at that? Are there pathophysiologies that underlie those different [types]?
Aaron Gerds, MD: That’s a great question, especially on the heels of some of the things that Srdan [Verstovsek, MD, PhD,] said about a bone marrow biopsy being the core part of this, and then connecting that with what you see clinically. We like to make nice discrete bins for diagnoses, but diseases are a smear in real life. Sometimes it’s difficult to separate different things. Then we put everything into this bin of myelofibrosis, but there may be different subtypes of patients. We all experience that every day in our clinics. No 2 patients are alike.
There are some ideas about how we can separate different subsets of patients within myelofibrosis. Then I’d go even further to say that there are other diseases that can lead to scar tissue in the bone marrow. Some older reports suggest that upward of 30% of patients with myelodysplastic syndromes will have some fibrosis in their bone marrow. Of course there are other diseases that aren’t malignancies that can lead to scar tissue in the bone marrow: the secondary myelofibrosis from rheumatologic or inflammatory disorders or even infectious disease. That clinical history is super important.
There’s a concept of primary vs secondary. Sometimes we use the term secondary myelofibrosis to describe those inflammatory-related nonmalignant myelofibrosis cases, but we often use the term secondary myelofibrosis as well to describe post-ET [essential thrombocythemia] and post-PV [polycythemia vera] myelofibrosis, where myelofibrosis has become a later stage or a new evolution of someone’s ET or PV. That’s in contrast with primary myelofibrosis, where the diagnosis of myelofibrosis is made at the beginning of clinical presentation and the workup.
There’s also an emerging concept of cytopenic vs proliferative or myelodysplastic vs myeloproliferative types of myelofibrosis. That’s getting toward what we’re seeing in the blood when we look at blood counts, as well as what we see when we look at the bone marrow. A patient with cytopenic myelofibrosis would have anemia, thrombocytopenia, and sometimes even neutropenia as part of their peripheral blood counts. When we look in the bone marrow, we can sometimes see even hypocellular marrows. With the more proliferative type of myelofibrosis, we see preserved counts or even elevated platelet counts—platelet counts in particular—as well as red blood cell counts, so less anemia. We often see a higher white blood cell count in those patients, too. You can separate these bins a little within myelofibrosis.
There are some underlying pathophysiologic differences between these vague groups of patients. Patients with cytopenic myelofibrosis are more likely to have primary vs post-ET or post-PV myelofibrosis. Patients with cytopenic myelofibrosis are more likely to have lower variant allele frequencies or allele burden of their JAK-STAT mutation that’s driving the disease. Cytopenic myelofibrosis is also more likely to have second or third mutations in the myelofibrosis cells, so the next-generation sequencing panels that Srdan mentioned can be helpful in looking at some of these cases a little more deeply. The response to therapies may be different as well. The focus on these different subtypes of patients has become more important because we now have more therapies available to us in the clinic, and we want to best understand how to use them.
Transcript edited for clarity.