Large granular lymphocytic (LGL) leukemia is a rare type of blood cancer. It affects specific types of white blood cells that develop in the bone marrow — either T cells or natural killer cells — which are both important for fighting off infections. People with LGL leukemia produce too many of these cells, and the cells that are made contain abnormalities. The cells are too big and contain small particles called granules. These abnormal cells may crowd out other normal blood cells and fail to stop infections.

LGL leukemia is very rare. Studies have found that this disease is diagnosed at a rate of 0.2 cases per 1 million people per year. LGL leukemia is equally likely to affect men and women. It is most often found in people who are between the ages of 45 and 75, and the average age at diagnosis is 60.

How Does Large Granular Lymphocytic Leukemia Differ From Other Types of Leukemia?

There are many different types of leukemia. Firstly, leukemia is classified as either acute or chronic. Acute leukemia involves immature cells that grow quickly. Chronic leukemia involves cells that are more mature, can function a little more normally, and grow more slowly.

Secondly, leukemia is classified as either myeloid or lymphoid. Myeloid leukemia, also called myelogenous leukemia, affects myeloid blood cells, which include red blood cells, platelet-producing cells, and certain types of white blood cells. Lymphoid or lymphocytic leukemias affect white blood cells called lymphocytes, which are involved in the immune system.

The most common types of leukemias are:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Chronic lymphocytic leukemia (CLL)

However, LGL leukemia doesn’t quite fall into any of these categories, though it is most closely related to chronic lymphocytic leukemia (CLL). The main difference is that CLL primarily affects lymphocytes called B cells. LGL leukemia affects either T cells (also called T lymphocytes) or natural killer cells.

There are two subtypes of LGL leukemia, depending on which cell type is affected. One is T-cell large granular lymphocytic leukemia, also called T-cell LGL or T-LGL leukemia. The other is natural killer large granular lymphocytic leukemia, also called NK-cell LGL or NK-LGL leukemia.

T-LGL is more common than NK-LGL, making up more than 85 percent of total cases of LGL leukemia. Both T-LGL and NK-LGL have similar symptoms and treatment plans.

Symptoms of Large Granular Lymphocytic Leukemia

LGL leukemia symptoms are similar to those of other leukemias. Most people with LGL leukemia already have symptoms by the time they are diagnosed. These symptoms may vary slightly from person to person, and not everyone will experience the same ones.

Some of the signs and symptoms of large granular lymphocytic leukemia are:

• Neutropenia, which is a low number of another type of white blood cells called neutrophils
• Lymphocytosis, a high number of lymphocytes
• Anemia, a low number of red blood cells
• Thrombocytopenia, a low number of platelets
• Fever
• Night sweats
• Unintentional weight loss
• Recurrent infections

Additionally, 25 percent to 50 percent of people diagnosed with LGL leukemia have an enlarged spleen (splenomegaly). The spleen is an organ in your abdomen that helps remove and recycle old or damaged blood cells. Some people with the condition also have an enlarged liver or swollen lymph nodes (lymphadenopathy), although both are uncommon.

Diagnosis of Large Granular Lymphocytic Leukemia

Your doctor will likely perform several laboratory tests before making a diagnosis of LGL leukemia. They will also probably give you a physical exam and ask you about your personal and family health history.

Your doctor may perform tests such as:

• A complete blood count (or CBC), which provides information about how many of each type of blood cell you have
• A peripheral blood smear, for which a doctor will look at the cells in a sample of your blood through a microscope
• A bone marrow aspirate or biopsy, for which a sample of bone marrow tissue is removed for a better analysis of your blood cells
• Flow cytometry, which is a test of cells from your blood or bone marrow that are analyzed with antibodies to determine which type of cell — T cells or natural killer cells — is affected

LGL leukemia also shares many symptoms with other types of blood disorders. Because LGL leukemia is so rare, it’s possible for a doctor to mistake this disease for another form of cancer or a different blood condition.

What Causes Large Granular Lymphocytic Leukemia?

Like all types of cancer, LGL is caused by genetic mutations. Some of these mutations are inherited, passed down from parents to children, and present in all of their cells from birth. Other mutations are acquired, meaning they happen over the course of a person’s life and are only found in some cells.

Scientists have identified some of the gene mutations that are commonly found in LGL leukemia. For example, many people with LGL leukemia have STAT3 mutations. However, doctors don’t yet fully understand why certain people get these gene mutations, nor why these genes can cause LGL leukemia.

Some people may be more at risk of developing LGL leukemia. In general, a person’s risk for developing all types of leukemia can be increased by factors such as obesity or exposure to radiation or chemicals. Additionally, having an autoimmune disease may be a specific risk factor for LGL leukemia. About 20 percent of people diagnosed with this cancer have a history of rheumatoid arthritis or another autoimmune condition.

Some people with LGL may have some of these risk factors; others may have none. There is no certain way to prevent leukemia from developing, and it’s often not clear why any one person develops the disease.

Treatments for Large Granular Lymphocytic Leukemia

There are several different treatments for leukemia. Your doctor may prescribe different types at different points in time.

If your LGL leukemia is not growing very quickly and is not symptomatic (indolent), your doctor may not give you any treatment, and may instead use a “wait-and-watch” strategy. This approach involves keeping an eye on your blood counts and your symptoms. Most people with LGL leukemia need treatment eventually.

There are several types of treatment options for LGL leukemia, including:

• Immunosuppressive therapy with drugs such as Trexall (methotrexate), which can block immune cells and slow down proliferation (growth) of cancer cells
• Cytoxan (cyclophosphamide), a chemotherapy drug often used to treat blood cancers, which may help increase levels of red blood cells
• Cyclosporine, a treatment that blocks cancerous immune cells and can help raise the levels of certain other types of white blood cells

If you start one or more of these medications, your doctors will likely monitor you over time to see how well the treatments work. If your cancer is refractory — unresponsive to medication — your doctor may switch you to a different treatment. On the other hand, if your cancer responds well to the prescribed drugs, you may continue taking them long-term.

Some people with LGL leukemia may also undergo surgery to remove their spleen (splenectomy). Others may receive a stem cell transplantation, which involves destroying the damaged bone marrow and replacing it with bone marrow from a healthy donor. The transplant may help some people stop producing cancerous cells.

Treatment Side Effects

Some LGL leukemia medications can cause side effects, including:

• Tiredness
• Nausea
• Diarrhea
• Mouth sores
• Bleeding problems
• Cytopenias, which are low levels of different types of blood cells

Leukemia and Mental Health Treatment

Just as it is important to receive treatment for your physical health, it is also important to address your mental health. Many people diagnosed with leukemia also develop anxiety and depression. Anxiety and depression may look like feelings of sadness or hopelessness, but they can also involve fatigue, irritability, and sleep and appetite problems.

People living with depression may also have worse cancer-related symptoms, so getting treatment is important. Talk to your doctor if you have concerns about your mental health.

LGL Leukemia Outlook

People with LGL leukemia live for an average of 9 to 10 years following diagnosis. One of the leading causes of death is severe infection, a result of the immune system impairments found in people with LGL leukemia.

New treatment options for LGL leukemia are regularly being developed. People with LGL leukemia can ask their doctors about clinical trial options. If you participate in a clinical trial, you may receive new treatments that are more effective than current treatments.

Connect With Others

Living with cancer may be easier with the support of others who understand what you’re going through. MyLeukemiaTeam is the social network designed for people living with leukemia and their loved ones. Every day, more than 8,000 members connect to ask for advice and share their experiences of life with leukemia.

Do you have large granular lymphocytic leukemia? What advice do you have for others with the condition? Comment below or start a conversation on MyLeukemiaTeam.