Large Granular Lymphocytic Leukemia

What is large granular lymphocytic leukemia (LGL)?

Large granular lymphocytic leukemia (LGL) is a rare type of chronic leukemia that affects white blood cells known as lymphocytes. Lymphocytes fight viruses and make antibodies that help fight infection.

There are two types of large granular lymphocytic leukemia —T-cell large granular lymphocytic leukemia (T-LGL) and chronic lymphoproliferative disorder of NK-cells (CLPD-NK). These conditions start in white blood cells called cytotoxic T-cells or natural killer cells. Both types of large granular lymphocytic leukemia grow slowly. They typically affect people age 60 and older. Healthcare providers can treat LGL, but the condition sometimes comes back and can become a chronic health issue.

How does this condition affect my body?

LGL is a type of chronic lymphocytic leukemia that occurs when certain T-cells and natural killer cells mutate, becoming abnormal cells that keep your bone marrow from producing normal blood cells. People with LGL often develop neutropenia, meaning they produce low numbers of granulocytes (the most common white blood cells) and have an increased risk of infection. They may also develop anemia, which happens because LGL cells affect red blood cell production.

Who does it affect?

Large granular lymphocytic leukemia is very rare, affecting 1 in 1 million people across the world. Most people are in their 60s when they’re diagnosed.

What are the symptoms of large granular lymphocytic leukemia?

People may have this condition and never have symptoms. One study showed about one-third of people with LGL didn’t have any symptoms when they were diagnosed. Instead, they learned they had LGL because blood tests showed they had unusually low red blood levels or low levels of neutrophils (a type of granulocyte). In some cases, people are diagnosed with LGL because they’re being treated for blood disorders and they have symptoms that healthcare providers link to large granular lymphocytic leukemia. People who do have symptoms often have the following:

• Fatigue: Extreme tiredness is the most common LGL symptom and is likely due to anemia.
• Frequent fevers and recurring infections: People have fevers caused by bacterial infections.
• Enlarged spleen (splenomegaly): Infections and some types of anemia may cause your spleen to become enlarged.

What conditions are linked to large granular lymphocytic leukemia?

Many people with LGL have autoimmune diseases, particularly rheumatoid arthritis. Other common conditions are:

• Anemia: This condition means you don’t have enough healthy red blood cells and hemoglobin. Many times, people have severe anemia and rely on blood transfusions to maintain red blood cell levels. Some people with LGL have hemolytic anemia, which happens because red blood cells are destroyed and not because of low red blood cell production.
• Lymphocytosis: This is having a high lymphocyte (white blood cell) count. People who have lymphocytic leukemias or lymphomas and viral infections usually have low lymphocyte counts.

What causes large granular lymphocytic leukemia?

Healthcare providers aren’t sure what causes the condition, but they believe there’s a link between this type of leukemia and immune responses, autoimmune diseases or other cancers:

• About 30% of people with this condition also have rheumatoid arthritis and other autoimmune diseases.
• Another 25 % to 30% have another kind of lymphoma or other kinds of cancer.
• Many people with this condition also carry mutated forms of two genes — STAT3 and STAT5B — that play roles in cell immunity and how cells divide and multiply.

How do healthcare providers diagnose large granular lymphocytic leukemia?

Healthcare providers typically do blood tests and genetic analyses to diagnose this condition. Common tests may include:

• Complete blood count (CBC) with differential: A CBC with differential is a measure of all of your blood cells, including the number of each type of white blood cell.
• Peripheral blood smear: This is a technique healthcare providers use to examine blood cells under a microscope so they can count the number of LGLs in your blood.
• Flow cytometry: This lab test analyzes cell characteristics. Healthcare providers often use this test to diagnose and classify types of leukemia.
• Immunophenotyping: Healthcare providers analyze blood or tissue samples for signs of markers on cell surfaces. Markers indicate specific types of certain conditions.
• T-cell receptor (TCR) gene rearrangement analysis: Healthcare providers use these blood or bone marrow tests to look for problems in the genes that control how your T-cells work.
• Genetic testing: Healthcare providers may test for STAT3 and STAT5 gene mutations.

They may do other tests, including bone marrow examinations, to rule out conditions including immunodeficiency, rheumatoid arthritis, myelodysplasia and myeloid mutations. They may also check immunoglobulin levels and monoclonal protein levels.

How do healthcare providers treat large lymphocytic granular leukemia?

If you have T-LGL or CLPD-NK leukemia but don’t have symptoms, your provider may recommend watchful waiting. In watchful waiting, providers monitor your health, typically taking blood tests every few months and watching for signs of symptoms.

People who do have symptoms may receive immunosuppressive therapy and steroids. Healthcare providers may use one treatment after another or use low-intensity forms of treatment. Because LGL is a rare condition, people often seek out doctors who specialize in this disease.

Can I reduce my risk of developing this disease?

No, you can’t. Healthcare providers don’t know the exact cause of large lymphocytic granular leukemia, so they can’t say how you might avoid it. That said people who have autoimmune diseases have an increased risk of developing this condition. If you have an autoimmune disease, ask your healthcare provider whether you should be concerned about developing LGL.

Is large granular lymphocytic leukemia a fatal illness?

Most of the time, large granular lymphocytic leukemia is a chronic illness that isn’t fatal. About 75% of people with T-LGL leukemia and CLPD-LGL leukemia are alive five years after diagnosis. About 10% of people with these types of leukemia die of severe infections that are complications of leukemia.

How do I take care of myself?

If you have a type of large granular lymphocytic leukemia, you may not have symptoms but you should take steps like monitoring your overall health and having regular checkups. Regardless of whether you have symptoms, the following suggestions may be helpful:

• Eat a healthy diet of lean protein, fruits, vegetables and whole grains.
• Exercise regularly.
• Get enough rest.
• Manage your stress.
• Protect your immune system: Ask your provider about vaccinations and other things you should do to avoid infection.

Can you live a normal life with this condition?

In general, people treated for LGL can typically live normal lives and have the same lifespan as people who don’t have the condition. It’s important to remember that some people who have LGL already have serious blood disorders that affect their quality of life.

When should I see my healthcare provider?

You should see your healthcare provider if you develop symptoms that may be signs your condition is getting worse. If you have symptoms and are receiving treatment, you should see your provider if you notice changes in your body, such as symptoms that are getting worse.

What questions should I ask my healthcare provider?

Large granular lymphocytic leukemia is a very rare illness. Here are some suggested questions that may help you learn more about LGL:

• What type of LGL do I have?
• What are treatments?
• Will I need more than one kind of treatment?
• I feel fine. Will I have symptoms?
• I have other medical conditions. Will LGL make them worse?

A note from Cleveland Clinic

Large granular lymphocytic leukemia (LGL) is a rare blood cancer that affects your white blood cells. You can have this condition but not notice any changes in your body that may be LGL symptoms. In some cases, people may not have symptoms for several years. Healthcare providers can’t cure the condition, but they have treatments to manage its symptoms. It may be alarming to hear you have an incurable illness. Your healthcare providers will understand why you may worry about what’s next. They’ll be glad to explain what you can do now to support your health and what you can expect when you do have symptoms. Knowing what to expect may help you feel more confident about living with LGL.