Chronic neutrophilic leukemia (CNL)

CNL is a myeloproliferative neoplasm. That is a group of blood cancers in which the marrow makes too many of certain blood cells. In CNL, the extra cells are mature neutrophils, the white cells that fight infection. They look normal under a microscope, but there are far too many of them.

CNL is very rare and mostly affects older adults. It is different from chronic myeloid leukemia (CML): CNL does not have the Philadelphia chromosome or the BCR::ABL1 gene change that drives CML.

A high neutrophil count is much more often caused by an infection, inflammation or medicines such as steroids, so doctors rule those out first. Diagnosis uses blood counts, a bone marrow biopsy and gene tests. Finding a CSF3R change is a key part of the diagnosis.

Most people with CNL have a change in the CSF3R gene. This gene makes a receptor, a kind of switch, that tells the marrow to produce neutrophils. When the gene is changed, the switch stays on, so the marrow keeps making more. The most common change is called T618I.

In most people, this change happens during life and only in blood-forming cells. It is not caused by anything the person did. Other gene changes, such as in ASXL1 or SETBP1, often appear alongside it and can affect how the disease behaves.

Very rarely, a CSF3R change is inherited and CNL runs in a family. One reported family had people with CNL across four generations.

Many people have no symptoms at first. CNL is often found when a routine blood test shows a very high white cell count. Others notice tiredness, bone pain, itching, easy bruising or gout.

The spleen often grows larger, and sometimes the liver does too. A large spleen can cause a feeling of fullness in the belly. Bleeding is a known risk in CNL. In rare cases, it has happened even when platelet counts were not low.

How fast CNL changes differs a lot from person to person. In some people it turns into a fast-growing acute leukemia, which is much harder to treat. Doctors use blood counts and gene results, such as an ASXL1 change, to judge each person’s risk.

Living with CNL often means regular blood tests, pills to control blood counts and checks on the size of the spleen. Some people feel well for long stretches. Others deal with tiredness, itching, bone pain, bleeding or side effects from treatment.

Because CNL is so rare, the research is small and there is no set plan to follow. People may be referred to a center that treats myeloproliferative neoplasms for gene testing, a clinical trial or a transplant opinion. Living with that uncertainty can be hard for patients and families.

If a transplant is planned, it means conditioning, weeks in or near the hospital while the new cells engraft, and months of close follow-up. The team watches for infection, graft-versus-host disease and any sign that CNL has returned.

A donor transplant for CNL uses healthy blood-forming cells from another person. In the CIBMTR and EBMT study, most donors were either a fully matched brother or sister or a well-matched unrelated registry volunteer. Counting every unrelated donor, just over half of the transplants used one.

Many people with CNL are older, and not everyone has a brother or sister who matches and is healthy enough to donate. A registry volunteer can make a transplant possible when no family donor fits. Timing can matter, because a transplant works less well once CNL has turned into acute leukemia.