Myelofibrosis and its Clinical Phenotypes


An explanation of the clinical phenotypes of myelofibrosis.

Case: A 67-Year-Old Man With Myelofibrosis

Initial presentation

RF is a 67 y/o man who visits his primary care physician for his yearly checkup. He reports having fatigue and bone pain for the last few months. More recently, he’s been complaining of abdominal discomfort which he thinks is probably related to the big Thanksgiving dinner party, he and his wife hosted.

He enjoys spending time working on antique cars in his garage, but his wife says he becomes tired after just an hour.

RF has not noticed any changes in his eating habits, but his wife mentions he doesn’t eat as much as he used too. Upon examination, RF has lost close to 13 lbs. since this last yearly exam.


Primary myelofibrosis diagnosed about 1 year ago

Diabetes (controlled with diet and exercise)


SMH: Smoked 3 packs/day but quit 5 years ago; he drinks occasionally

PE: abdominal exam reveals spleen palpable 5cm below left coastal margin, visible bruising

Initial Labs/Workup:

Platelet count: 184 x 109/L

Hgb: 10g/dL

WBC: 34 x 109/L

Bone Marrow Biopsy

Shows an increase in megakaryocytes

Bone Marrow Fibrosis

Megakaryocyte Atypia

Molecular testing

JAK-V617F mutation: positive

Initial treatment:

Patient was started on ruxolitinib 10mg BID when initially diagnosed

Current Presentation/Labs:

One year later, RF reports increasing fatigue and abdominal pain)

Current Labs:

Platelet count: 57 x 109/L

Hgb: 8g/dL

WBC count: 29 x 109/L

Raajit Rampal, MD, PhD: Now let's talk more about myelofibrosis and its phenotypes. There are different clinical phenotypes that we can see in patients with myelofibrosis. To break this down simply, there are patients with more proliferative disease as evidenced by higher blood counts such as an elevated white blood cell count and elevated platelet count. There are patients who have more of what's called the cytopenic phenotype. These are the patients who can present with pancytopenia on 1 extreme, or perhaps thrombocytopenia and anemia. This has been studied and there do seem to be some differences in such patients. There does seem to be more of an evolution from ET [essential thrombocythemia] or PV [polycythemia vera] in patients with more proliferative types of myelofibrosis. For example, oftentimes it evolves from polycythemia to myelofibrosis. Their red blood cell count and hemoglobin may still be somewhat higher than would be expected in a typical myelofibrosis patient.

There are other factors to consider. Mutation types may differ between cytopenic and proliferative diseases. Spleen sizes can differ as well as the propensity for patients to have bad outcomes. We see this more often in patients with cytopenic myelofibrosis. By bad outcomes, what I'm referring to specifically are progression to acute leukemia as well as bone marrow failure, and ultimately, death. What has been established in a number of studies is that thrombocytopenia in and of itself is associated with an increased risk of death. And anemia, particularly transfusion-dependent anemia, is associated with a higher risk of death in myelofibrosis patients. It's important to recognize that the phenotypes of myelofibrosis can differ based on the counts, and that has implications for a patient’s prognosis. Coming back to our case, the patient RF had experienced fatigue and abdominal pain. The examination showed splenomegaly. The patient was started on ruxolitinib, 10 mg twice daily. But as we talked about a moment ago, the patient after about a year of treatment was noted to have profound thrombocytopenia and anemia and was having recurrent symptoms of fatigue and abdominal pain.

Transcript edited for clarity.

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