Educated Patient® MPN Summit Differentiating an Essential Thrombocythemia Diagnosis Presentation: May 7, 2022

When being diagnosed with a myeloproliferative neoplasm (MPN), it is crucial — though oftentimes difficult — to come to the proper diagnosis, especially when differentiating between two subtypes of the disease, pre-fibrotic myelofibrosis and essential thrombocythemia, according to Dr. Jamile M. Shammo, professor of medicine and pathology at Rush University Medical Center in Chicago.

“At times, arriving at the right diagnosis is not necessarily a simple black-and-white type thing. We as physicians and also patients need to deal with some degree of uncertainty and understand that MPNs have some degree of spectrum that we have to be comfortable with. But with that in mind, we have to also be cognizant of various diagnoses and diagnoses that may carry with them varied prognoses. It’s important to understand that,” Shammo said during CURE®’s Educated Patient® MPN Summit.

All subtypes of MPNs occur when the bone marrow is “hypercellular,” meaning that it produces too many cells. So if a patient has elevated blood counts, clinicians will first want to rule out other potential causes, such as inflammation, infection or iron deficiencies. After that, patients may undergo next-generation sequencing that could reveal a JAK mutation, which is highly indicative of MPNs.

Once it is determined that a patient does, indeed, have an MPN, clinicians may look at the characteristics of the cells in the bone marrow to help determine what kind of MPN it is.

Nowadays, there is more of an emphasis and research toward identifying essential thrombocythemia versus pre-fibrotic myelofibrosis, but that was not always the case.

Shammo explained that in the 1970s, researchers started to analyze the different outcomes in patients who were all diagnosed with essential thrombocythemia: some only had elevated megakaryocytes (cell clustering in the bone marrow that is common in MPNs), while others also had an increased amount of granulocytes (a type of white blood cell).

“They thought …If we applied a certain new designation (to patients labeled as having essential thrombocythemia), specifying those particular morphologic features, can we actually separate those patients into true essential thrombocytopenia and those who may actually fall into the category of pre-fibrotic myelofibrosis,” Shammo said.

An essential thrombocythemia diagnosis is fairly straightforward, with the following criteria:

• Platelet over 450
• Excluded other types of MPNs or myelodysplastic syndrome
• Evidence of a clone in the presence of a driver mutation
• Megakaryocytic proliferation
• Little fibrosis in the bone marrow

“This is essential to how patients (with essential thrombocythemia) should be diagnosed: by exclusion and by demonstrating that the bone marrow has very little fibrosis and just megakaryocytic lineage proliferation,” Shammo said.

Coming to a pre-fibrotic myelofibrosis diagnosis, on the other hand, can be “a little more complicated, because you have to show that the megakaryocytes are proliferating and have granulocyte proliferation,” according to Shammo.

Additionally, pre-fibrotic myelofibrosis tends to come with anemia as well, that cannot be explained by any other condition.

Even within the subset of patients who have pre-fibrotic myelofibrosis, there are different categories that can determine what kind of treatment they undergo. Those with low risk may be eligible for observation only, while those with intermediate risk (those with estimated survival averages of 10 years or more) can have their therapy focus on symptoms and perhaps consider participation in clinical trials. Those with high-risk disease, however, (with an estimated average survival time less than five years) will have intensive treatment, potentially stem cell transplant or clinical trial participation.

Though difficult, differentiating between essential thrombocythemia and pre-fibrotic myelofibrosis is important, because the two can come with vastly different outcomes. Shammo noted that prior research found that pre-fibrotic myelofibrosis tended to be more likely to progress to overt myelofibrosis and have poorer leukemia-free survival rates.

“Pre-fibrotic myelofibrosis has a better prognosis than those who have full-blown primary myelofibrosis, but it’s a bit worse than those patients who have (essential thrombocythemia),” she said.

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