Welcome to Managing MDS. My name is Rami Komrokji and I am Professor of Oncologic Sciences and Clinical Director in the Malignant Hematology Department at the Moffitt Cancer Center. I am frequently asked about making the diagnosis of chronic myelomonocytic leukemia (CMML), or when we see myelocytosis how do we make the diagnosis? This is very related to patients with myelodysplastic syndromes (MDS) as well as patients with myeloproliferative neoplasms. CMML used to be part of the subtypes of MDS. In the new WHO classification there is a group called myelodysplastic/myeloproliferative diseases where CMML is the most common subtype of that group. In patients where there is proliferative CMML, which means the white blood cell count is increased, those are easy to tease out from straightforward myelodysplastic syndromes. However, in non-proliferative CMML where the white blood cell count is often below 10,000, I think it is the increase in the monocytes that makes that distinction. By the WHO criteria, dysplasia is sometimes not even required to make a diagnosis of CMML, which is different from the other types or subtypes in MDS. Presence of persistent monocytosis, more than three months without active cause, is adequate to make a diagnosis of CMML. One of the important points is to look at the differential diagnosis and make sure those monocytes are more than 10% because it is not just absolute monocyte count. Particularly when the white blood cell count is high, it is easy to reach that 1,000 absolute monocyte count that is required by the WHO for diagnosis of CMML, but it usually has to be more than 10%. Nowadays, we are starting to have some complementary tests in making the diagnoses of CMML. For example, data from somatic gene mutations or next-generation sequencing can help us. Although they are not part of the diagnosis, there are certain mutations frequently encountered in patients with CMML and they happen together. For example, when we see patients with monocytosis and we see evidence of a TET2 and SRSF2 mutation by NGS, then that is a complementary piece of information to the diagnosis. There have also been suggestions of certain uses for flow cytometry, that there are patterns where we could distinguish the monocytes, whether they are inflammatory or primary monocytes in CMML, so we are starting to incorporate those. In summary, I think if patients have proliferative CMML then there will be leukocytosis, which should not be seen typically in MDS. In non-proliferative CMML, if patients have resistant monocytes, more than 1,000 (10% of the differential), that is suggestive of CMML. Nowadays we complement that by looking at data from next-generation sequencing and some data from flow cytometry that would tell us those monocytes are not reactive.
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