Chronic myelomonocytic leukemia (CMML)

Diagnosis starts with a complete blood count (CBC) and a hand count of the white cells (manual differential). This shows how many cells are monocytes and how many are immature cells called blasts. Under the 2022 World Health Organization (WHO) rules, monocytes must stay high: at least 500 per microliter, and at least 1 in 10 white cells. European guidance says older blood counts, if available, are used to show the rise has lasted more than 3 months. Doctors also look for other causes of high monocytes, such as long-lasting infections or autoimmune disease.

A bone marrow test (aspiration and biopsy) takes a small sample of liquid marrow and bone, from the hipbone or breastbone. It shows the share of blasts and signs of abnormal cell development (dysplasia). Chromosome tests (cytogenetics) and gene tests look for changes picked up during life. Changes in the ASXL1, NRAS, RUNX1 and SETBP1 genes feed into CMML risk scores. Tests also rule out the BCR::ABL1 change (the Philadelphia chromosome) that defines chronic myeloid leukemia. A blood test called flow cytometry, which sorts monocytes into types, can help tell CMML apart from a harmless rise in monocytes.

The results set the subtype. A white count under 13,000 per microliter means the myelodysplastic type (MD-CMML); 13,000 or more means the myeloproliferative type (MP-CMML). The share of blasts sorts CMML into CMML-1 or CMML-2. A pathologist typically sends a biopsy report within about 10 days, and some test results may come in separate reports.

Lower-risk disease with few symptoms may be monitored or managed with supportive care. Transfusions and anemia-directed medicines can help selected patients. Hydroxyurea may reduce excessive blood counts and spleen-related symptoms in proliferative disease.

Azacitidine or decitabine may reduce disease burden or improve blood counts. More intensive therapy is used in selected circumstances, including some patients with a high blast burden. Non-transplant treatment and clinical trials may be appropriate when transplant is not a good fit.

A donor (allogeneic) stem cell transplant is the only treatment that may cure CMML, but it is not right for everyone. A large international study of people aged 18 to 70 diagnosed from 2000 to 2014 found that, in lower-risk CMML, having a transplant before the disease turned into AML shortened survival on average. The authors said a transplant may be considered for higher-risk CMML. Some people go straight to transplant, while others have treatment first.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

CMML behaves very differently from one person to the next. For some people it moves slowly for a long time; for others it moves fast. Care teams use CMML-specific risk scores that combine blood counts, the share of blasts, transfusion needs, chromosome results and gene changes. The National Cancer Institute says about 15 to 20 in 100 people with CMML go on to develop acute leukemia.

Age and general health shape the choices. CMML is usually diagnosed after age 70. A donor transplant carries real risks. In a large international study, people with lower-risk CMML who had a transplant before their disease turned into AML lived less long on average than those who did not. With higher-risk CMML, survival looked better with transplant, though the difference was not statistically certain. In European registry data, people who were in remission at transplant did better.

These figures describe groups, and many people in them were treated years ago. They cannot say what will happen to any one person. The risk group, and whether it changes over time, is what most often guides when a transplant is discussed.