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Chronic Neutrophilic Leukemia: An Overview

Posted on March 25, 2021
Medically reviewed by
Todd Gersten, M.D.
Article written by
Maureen McNulty

Chronic neutrophilic leukemia (CNL) is an extremely rare type of leukemia. Only about 200 cases of this blood cancer have ever been found. About two out of three people with CNL are male. People with CNL are an average of 65 years old when diagnosed. Treatments can help keep this disease under control for many years, but CNL sometimes transforms into a more aggressive form of leukemia and becomes more difficult to treat.

What Is Chronic Neutrophilic Leukemia?

CNL is a type of myeloproliferative neoplasm (MPN). MPNs are blood cancers in which the bone marrow makes too many of one type of blood cell. People with CNL have high levels of neutrophils (white blood cells that kill germs). Having high levels of neutrophils is called neutrophilia. The neutrophils in CNL are clonal, which means that they all contain identical gene changes and arise from the same parent cell.

CNL is similar to a few other types of blood cancers, including chronic myeloid leukemia (CML), atypical chronic myeloid leukemia (aCML), and chronic myelomonocytic leukemia (CMML). These other cancers also lead to high levels of neutrophils or other types of white blood cells (WBCs). However, these diseases have different underlying genetic causes or lead to different signs and symptoms other than CNL.

Causes of Chronic Neutrophilic Leukemia

Scientists have recently discovered some of the gene changes that lead to chronic neutrophilic leukemia. As many as 90 percent of people with CNL have mutations in a gene called colony-stimulating factor 3 receptor (CSF3R). A CSF3R mutation causes neutrophils to grow too quickly. Now that scientists know about this gene mutation, they may be able to better help people with CNL. The CSF3R mutation makes it easier for doctors to diagnose the disease, and may eventually help researchers come up with new medications that can target CNL cells.

Other gene mutations often found in CNL cells include the following genes:

  • SETBP1
  • SRSF2
  • U2AF1
  • TET2
  • ASXL1

Signs and Symptoms of CNL

Symptoms of chronic neutrophilic leukemia don’t usually appear early on in the disease. In later stages of CNL, people may experience:

  • Feeling more full than usual after eating
  • Fatigue
  • Sore throat
  • Feeling generally sick
  • Weight loss
  • Fever

Diagnosis of CNL

Signs of CNL may be discovered during routine physical exams, or they might be uncovered with diagnostic tests after leukemia symptoms appear. Signs that may point to CNL from a blood test include:

  • Low levels of red blood cells (anemia)
  • Normal or slightly decreased levels of platelets (thrombocytopenia)
  • Increased levels of the lactate dehydrogenase (LDH) enzyme
  • Increased levels of vitamin B12
  • Increased levels of the leukocyte alkaline phosphatase (LAP) enzyme

These signs are more likely to be caused by other health conditions. Having these disease indicators does not necessarily mean you have CNL. The World Health Organization has identified several other features that are usually found in people with chronic neutrophilic leukemia. You must have these characteristics in order to be diagnosed with CNL:

  • A WBC count higher than 25,000 cells per microliter
  • High levels of neutrophils in the bone marrow
  • Fewer than one percent of the WBCs in the blood that are blasts (immature cells), and fewer than five percent of the cells in the bone marrow that are blasts
  • An enlarged spleen and liver (hepatosplenomegaly)
  • No signs of reactive neutrophilia, meaning neutrophil levels aren’t increased because of other causes, such as a tumor or autoimmune disease
  • No signs of other blood disorders, including myelodysplastic syndrome (MDS) or other types of MPNs
  • No gene changes that may be a sign of other blood disorders, including BCR-ABL, PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2

Doctors measure these signs using blood and bone marrow samples. Your doctor may recommend that you get bone marrow tests to study the cells there. Bone marrow tests include a bone marrow aspiration and biopsy, in which a doctor removes bone marrow cells and fluid from inside of your hip or breastbone.

Your blood and bone marrow samples can be examined in a laboratory to identify gene changes. Tests that may be used to study your genes include karyotyping, cytogenetics, and polymerase chain reaction (PCR) tests. Knowing which gene changes are found in your cells can help your doctor confirm which type of leukemia you have and determine which treatments may be most effective.

Chronic Neutrophilic Leukemia Treatment

There is no one standard treatment for CNL. Because it is so rare, it is difficult to study. Most chronic neutrophilic leukemia treatments aim to reduce disease symptoms. If you have CNL, your doctor may initially recommend that you undergo chemotherapy. However, CNL sometimes becomes resistant to chemotherapy drugs, and sometimes it transforms into acute myeloid leukemia (AML), a more severe, faster-growing cancer. In these cases, you may have to switch treatment plans.

Immunotherapy

Intron A (interferon alfa-2b) is also sometimes used to treat CNL. This drug boosts the immune system, encouraging the body’s immune cells to fight off the cancer cells. Interferon alfa-2b is the only drug that has helped people with CNL go into long-term remission. Remission is when you no longer exhibit any signs of disease.

Chemotherapy

CNL is most often treated with Hydrea (hydroxyurea or hydroxycarbamide). Hydroxyurea can decrease levels of WBCs and make the spleen smaller. Hydroxyurea can often keep CNL under control during earlier disease stages. About three out of four people who use this treatment experience reduced symptoms. However, some people with CNL become resistant to hydroxyurea and may need to try a different treatment. Other chemotherapy drugs that may treat CNL include Leustatin (cladribine), Thalomid (thalidomide), Cytosar-U (cytarabine), and a category of medications called anthracyclines.

Targeted Therapy

If chemotherapy does not effectively control CNL, Jakafi (ruxolitinib) may be used. Ruxolitinib belongs to a category of drugs called kinase inhibitors. It blocks kinase enzymes that are sometimes responsible for making cancer cells grow out of control. Ruxolitinib is approved by the U.S. Food and Drug Administration to treat other types of MPNs. It is not officially approved to treat chronic neutrophilic leukemia, but it has helped some people with CNL achieve positive outcomes and is being studied as a CNL treatment in clinical trials.

Stem Cell Transplant

A stem cell transplantation is the only treatment that may cure CNL. During a stem cell transplant, a person’s diseased blood cells are replaced with healthy ones. Chemotherapy is first used to kill most of the blood and bone marrow cells before a person receives a dose of new blood stem cells. These stem cells can produce new copies of all of the blood cells. New stem cells may come from a donor, or they may be the person’s stem cells that were collected and stored in advance.

Stem cell transplants have been used to treat a few cases of CNL. Some people who have received a transplant have gone into remission for several months, and others have gone into remission for several years.

Prognosis and Outlook for Chronic Neutrophilic Leukemia

People generally live for an average of two years following a diagnosis of CNL. However, people can live much longer and some have lived for more than 20 years after diagnosis.

Chronic neutrophilic leukemia may persist for many years, or it may transform into AML. About 10 percent to 20 percent of individuals with CNL eventually develop AML. This transformation often happens within two years of CNL diagnosis.

Researchers aren’t yet sure what factors are likely to lead to a worse CNL prognosis (outlook).

Some potential prognostic factors that are currently being studied include:

  • Having a very high white blood cell count (over 50,000 cells per microliter)
  • Having a mutation in the ASXL1 gene
  • Thrombocytopenia (low platelet levels)

Building Community

Chronic neutrophilic leukemia is very rare. Joining a community of people with leukemia can help you connect with others who have experienced some of the same diagnostic tests and treatments that you have.

On MyLeukemiaTeam, you can connect with people who have leukemia, as well as their loved ones. Join now to start a new conversation, or comment below to share your experience.

All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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