T-cell large granular lymphocytic (T-LGL) leukemia affects white blood cells called lymphocytes, which are part of the body’s immune system. The “T” means the leukemia starts in T cells.
In someone with LGL leukemia, lymphocytes are enlarged and contain granules visible under a microscope. The two types of LGL leukemia are T-cell (T-LGL) leukemia and natural killer cell (NK-LGL) leukemia. T-LGL leukemia is more common.
This article examines T-LGL and its symptoms, risk factors, diagnosis, and treatment. It also discusses the outlook for T-LGL leukemia.
In LGL leukemia, large granular cells called lymphocytes accumulate in the blood. This can lead to various symptoms, such as bleeding, anemia, and recurring infection.
Normally, when a person has a viral infection, specific lymphocytes called T cells recognize viral proteins and foreign antigens. In response, the T cells activate and make copies of themselves to fight the virus.
The T cells release toxic molecules to fight and kill cells the virus has infected. The T cells also release inflammatory signals called cytokines, which communicate to the body that a virus is present.
The body responds to the inflammatory signal by prioritizing functions that fight the virus, such as producing more virus-fighting lymphocytes instead of other types of cells, such as platelets or red blood cells.
Usually, once T cells have successfully fought a virus, they die to make room for other blood cells. The death of the T cells stops the inflammatory signal from the cytokines, and the body can return to a normal, resting state.
In people with T-LGL leukemia, however, the T cells do not die. The body keeps receiving inflammatory signals even though there is no virus for the body to fight.
The leukemic blood cells accumulate and continue to send inflammatory signals, which leaves less room for other types of blood cells. The signals also communicate to the body to produce fewer platelets, red blood cells, and neutrophils.
A variant form of LGL leukemia involves a specific T cell called CD8+.
CD8+ T cells are T cells that carry the co-receptor CD8. A co-receptor is a surface protein that makes antigen receptors more sensitive.
CD8+ T cells recognize antigens. Antigens are substances that trigger the immune system to produce antibodies. They play an important role in targeting and eliminating infected cells, including cancer cells, without harming healthy tissues.
Changes to CD8+ cells may pose a severe risk to a person’s health, as their ability to destroy infected cells while preserving healthy tissue
Symptoms of T-LGL leukemia can include:
- low production of red blood cells, called red cell aplasia
- low production of neutrophils, a type of white blood cell
- changes to blood cell counts
- enlarged spleen
- recurring infections
- night sweats
- weight loss
- enlarged liver (rare)
- swollen lymph nodes (rare)
Experts associate T-LGL leukemia with autoimmune diseases, such as rheumatoid arthritis. Doctors diagnose autoimmune diseases before the onset of LGL leukemia in around 20% of cases, according to the Leukemia and Lymphoma Society.
- an abnormally high white blood cell count
- low numbers of platelets, red blood cells, and neutrophils
- both of the above
LGL cells have a distinctive appearance. Doctors can typically detect them by examining the blood under a microscope.
Doctors can order several tests to determine levels of LGL in the blood for a definitive diagnosis. These tests may include:
- Complete blood cell count: This test measures the numbers of various blood cells, including white blood cells, platelets, and red blood cells. High numbers of lymphocytes and low numbers of other types of blood cells can indicate LGL leukemia.
- T-cell gene rearrangement: This is a genetic test to show a group of cells with the same T-cell receptor, which confirms they all came from the same parent cell.
- Flow cytometry: Doctors examine blood cells with antibodies to determine whether more LGLs are in the blood than usual.
- Bone marrow biopsy: A doctor may remove a sample of bone marrow to determine whether abnormal cells are present.
Treatment depends on the severity of the cancer and its symptoms. There is no standard treatment for LGL leukemia, but treatment may involve:
- an immunomodulatory drug called cyclosporine
- immunosuppressive therapy drugs, such as methotrexate
- an alkylating agent chemotherapy treatment called oral cyclophosphamide
If a person does not respond to these treatments, doctors may recommend other treatments, including:
- surgical removal of the spleen, called splenectomy
- drugs called purine analogs, such as fludarabine with mitoxantrone and dexamethasone
LGL leukemia typically progresses slowly. Although there is no standard treatment or cure for T-LGL leukemia, research from 2016 suggests the median time of survival after diagnosis is
The life expectancy may be shorter and the outlook less favorable for rare, aggressive T-LGL leukemia. Aggressive LGL leukemia does not usually respond well to treatment.
In T-LGL leukemia, T-cell lymphocytes accumulate in the blood and crowd out other types of blood cells.
The cells do not die off as they should to allow the body to return to a healthy state and for other types of blood cells to proliferate. The body remains in an inflammatory state with an overabundance of LGL cells. This can cause symptoms such as infection, bleeding, and anemia.
The CD8+ variant of LGL leukemia begins in T cells that carry the co-receptor CD8+. Damaged CD8+ T cells have a reduced ability to destroy infected cells while preserving healthy tissue.
Researchers have found associations between T-LGL leukemia and autoimmune disorders, such as rheumatoid arthritis.
There is no standard treatment or cure for T-LGL leukemia. Combining treatments may help slow its course. Because LGL leukemia is typically slow to progress, a person may survive for many years after diagnosis.