Dr Hobbs on the Distinctions Between Proliferative and Cytopenic Myelofibrosis

Even if we haven’t always recognized these two [cytopenic and proliferative] entities as different phenotypes, the risk scores have always paid attention to the cytopenias.

Gabriela S. Hobbs, MD, clinical director of the adult leukemia service and leader of the myeloproliferative neoplasm research program at Massachusetts General Hospital, as well as an associate professor of medicine at Harvard Medical School, discussed factors that distinguish proliferative myelofibrosis from cytopenic myelofibrosis and how these phenotypes relate to risk stratification in patients with newly diagnosed disease.

Differences between cytopenic and proliferative myelofibrosis can be seen through the lens of risk stratification scores, according to Hobbs. When assessing a patient with newly diagnosed myelofibrosis, several risk stratification scores can help inform prognosis and drive treatment decisions, Hobbs said, noting that the Dynamic International Prognostic Scoring System (DIPSS) is easy to apply at the initial visit and that the Mutation-Enhanced International Prognostic Scoring System (MIPSS) can be layered in once genetic testing results return, she noted. Although DIPSS incorporates karyotype, that component can sometimes be estimated even without cytogenetic information, she added.

According to Hobbs, one of the key factors of these risk scores has been the presence of underlying cytopenias. For example, tools as old as the International Prognostic Scoring System counted anemia and thrombocytopenia as markers of higher-risk disease, she explained.

A key difference between cytopenic and proliferative myelofibrosis is apparent from the first blood count, Hobbs said. Patients with proliferative disease typically present with high white blood cell counts, normal hemoglobin levels, and normal or elevated platelet counts, frequently accompanied by larger spleens and more constitutional symptoms, she stated. These patients are more likely to have had essential thrombocythemia or polycythemia vera that evolved into secondary myelofibrosis, Hobbs explained. Conversely, patients with cytopenic disease typically present with low blood counts, often lack splenomegaly or prominent systemic symptoms, and are more likely to harbor additional mutations beyond JAK2, CALR, and MPL, she continued.

Hobbs uses these distinctions primarily to guide risk stratification, emphasizing that patients with low blood counts generally fall into higher-risk categories, even before their values are formally entered into a scoring system. Recognizing the phenotype early, she concluded, allows clinicians to anticipate a patient’s likely disease course and tailor management accordingly.