Identifying the Categories of Myelofibrosis


Shifting their attention to myelofibrosis, Rami S. Komrokji, MD, and Pankit Vachhani, MD, define differences between various subsets of disease.


Pankit Vachhani, MD: We'll switch gears and talk about myelofibrosis. There are different words like primary myelofibrosis, secondary myelofibrosis. Now more so in the lexicon, we are hearing about proliferative myelofibrosis and then cytopenic or myeloproliferative depleted myelofibrosis. Dr Komrojki, can you take us through some of these words and what they mean, how you differentiate between these categories? And then what risk stratifications tool do you use in your practice?

Rami S. Komrokji, MD:As we said, myelofibrosis obviously is the most symptomatic disease out of the myeloproliferative neoplasms and unfortunately the one that impacts overall survival for patients the most. Obviously, we use terms primary and secondary, deferring if this is de novo myelofibrosis or secondary coming from polycythemia vera or essential thrombocythemia. As you know 10 to 15% of the patients roughly with ET or PV will end as myelofibrosis. There are some slight differences in the outcome, the mutation landscape between primary and secondary. Obviously, not to confuse sometimes we say reactive fibrosis in the bone marrow from other diseases as we mentioned earlier. But primary and secondary is term used to a de novo myelofibrosis or a myelofibrosis secondary is post ET or post PV myelofibrosis, which probably is better term than even secondary. And as you alluded, we revealed the underlying biology of the disease, confirming clinical observations for many years that those patients have different presentation with myelofibrosis. You have those patients that are predominantly proliferative, have high wide count, splenomegaly constitutional symptoms. Or you have that group that are cytopenic, present namely with cytopenia. There are some patients that technically don't have splenomegaly or constitutional symptoms. And the most difficult in my practice historically had been the patients that have a combination. They have slenomegaly that they need treatment, but then yet have profound cytopenia that limit some of the historical options we use for those patients. Now we use this term of cytopenic and proliferative myelofibrosis describing that. And it turns out that there are some differences in the landscape or the genomic landscape of those diseases. For example, patients with cytopenic myelofibrosis have lower JAK2 allele burden, they tend to be more primary. They have more enrichment with splicing mutations, like MDS. Proliferative myelofibrosis tends to have higher allele burden of JAK2, less of the splicing mutations, more of some signaling mutations. Now, as we mentioned, once we establish the diagnosis, the theme in all myeloproliferative diseases, like any oncology disease is the next step is risk stratification. Because that's your prognostic tool and that's sometimes how we tailor the treatment. In myeloid diseases in general, that's a tool also we are using, are we going to send those patients to transplant or not. And it gets complicated in myelofibrosis because there are several models. There are clinical models, now genomic models, hybrid models. You would have heard terms like international prognostic scoring system, IPSS, dynamic IPSS, IPSS plus, GIPPS, MIPSS, those are molecular mutations. The idea obviously that you are weighing on alarm score from certain factors. Most of those models will account for presence of constitutional symptoms, leukocytosis, circulating blasts, and importantly, anemia and thrombocytopenia and transfusion dependency are probably in all those models counted for as poor prognostic factors. The molecular models are enhanced by presence of mutations. Calreticulin is favorable, for example. Complex karyotype, bad cytogenetics are incorporated. Certain mutations like SXL1, SRSF2, IDH1, IDH2, UTF, the Q157, a hotspot are counted as bad prognostic mutations. Obviously, nobody expects a busy practitioner to memorize those models. The MIPSS70 is available online, can be easily calculated. Would give you a risk for the patient and the category and the estimate. But I would say the idea is obviously you are weighing some clinical variables, molecular variables. And the end, you put the patients into probably 2 major buckets, a lower risk, or a higher risk, or lower intermediate and higher. The intermediate and higher, we always are going to be asking obviously about the role of allogeneic stem cell transplant. But then in the rest of the patients, we are going to be asking about treatment, what options do we have.

Transcript edited for clarity.

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