Shared insight on the differential diagnosis of myelofibrosis, including advice for identifying primary versus secondary disease.
Stephen T. Oh, MD, PhD: As far as diagnosing myelofibrosis, it’s a little different compared with polycythemia vera [PV] and essential thrombocytopenia [ET]. Regarding patients with PV and ET, they could present with problematic symptoms or complications of the disease—some patients present with a thrombotic event—but oftentimes the initial diagnosis is prompted by the identification of abnormal blood counts on a routine CBC [complete blood count] test. In contrast, patients with myelofibrosis typically present because they’re having symptoms. That can be fatigue related to progressive anemia, night sweats, weight loss, symptomatic splenomegaly. That’s often what prompts the initial work-up that leads to the diagnosis. The diagnosis, of course, is based on performing a bone marrow biopsy and finding the characteristic features of myelofibrosis, including reticulin fibrosis in the bone marrow.
Ruben Mesa, MD: With myelofibrosis, the terminology has always been a bit confusing because you both have the illness of myelofibrosis, but myelofibrosis refers to scarring in the bone marrow. Indeed, I once wrote a paper helping to summarize over 40 terms used for what we now call primary myelofibrosis. The International Working Group for myelofibrosis decided on that term, but there have been 40 others—agnogenic myeloid metaplasia, among many others.
When we speak of secondary myelofibrosis, here’s where it gets a bit confusing…. For individuals who have the illness of myelofibrosis—…. and I once published on MPN [myeloproliferative neoplasm] myelofibrosis—this includes primary myelofibrosis, post polycythemia vera, and post essential thrombocythemia myelofibrosis. This clinical entity with splenomegaly and cytopenias is associated with mutations such as JAK2, CALR, and MPL. It risks progression to AML [acute myeloid leukemia] and myeloproliferative neoplasms with a disease burden.
When someone asks about secondary myelofibrosis, normally they’re referring to patients with post-ET and post-PV myelofibrosis, whom we consider to really be very similar in terms of the disease biology but also the disease burden. Our treatment algorithms largely have been similar. There may be some slightly different prognostic models between both. True secondary myelofibrosis are non-MPN-associated conditions in which fibrosis can occur. There are patients with myelodysplastic syndrome who can have secondary fibrosis, but they won’t have splenomegaly. They don’t have non-anemia-type symptoms. CML [chronic myeloid leukemia] sometimes causes fibrosis. Fibrosis sometimes has been seen in autoimmune disease. Concerning secondary myelofibrosis, if it’s post-ET and post-PV, it’s a similar issue to primary myelofibrosis. If it’s truly secondary to a different condition, it may be an epiphenomenon.
Transcript edited for clarity.