LGL (Large Granular Lymphocyte) Leukemia
Large Granular Lymphocyte Leukemia (LGL) is a rare form of blood cancer with only an estimated 1,000 new cases diagnosed in the United States each year.
Patients with LGL leukemia have enlarged white blood cells with large granules. These enlarged white blood cells affect the body’s ability to fight off infection. In normal blood 10-15 percent of the lymphocytes are large granular lymphocytes (LGLs).
LGLs have a characteristic appearance as shown in the above figure. They are larger than normal lymphocytes and contain pink granules. LGLs are part of the normal immune system and are killer cells, which fight viruses. Large granular lymphocyte leukemia occurs when there are too many LGLs and not enough of the other types of blood cells, especially the neutrophils. In some cases, the total number of lymphocytes is not greater than normal; however, the proportion or percentage of LGLs in your lymphocytes is higher than normal.
Blood consists of three types of cells:
- White blood cells which fight infection and disease
- Red blood cells which carry oxygen in the blood
- Platelets which help the blood to clot
There are several types of white blood cells:
- Granulocytes (including neutrophils, eosinophils, and basophils)
- Lymphocytes (including B-cells, T-cells, and NK-cells)
There are two types of LGL Leukemia:
- T-cell LGL Leukemia
- NK-cell LGL Leukemia
- Change in blood cell counts
- Repeated infections
- Frequent fevers
- Night sweats
- Unintended weight loss
- Enlarged spleen
- Enlarged liver (rare)
- Swollen lymph nodes (rare)
LGL leukemia can be diagnosed by conducting several tests, including:
- CBC (Complete Blood Count)
- Flow cytometry with an LGL Panel
- TCR (T-cell Receptor Gene Rearrangement)
- Bone Marrow Biopsy
- Splenectomy and spleen analysis
The hallmark of LGL leukemia is a high lymphocyte count and a low neutrophil count. This would be detected by the CBC and is usually the first indication that there might be something out of the ordinary. The flow cytometry is one of the main diagnostic tests. It employs an array of activation markers that will indicate if a certain level of LGLs are present and what type of LGLs. This will help to narrow down the type of LGL a person might have.
Unfortunately, not all hospitals have flow cytometry available and even those that do may not be familiar with the panel of markers that are commonly used for LGL leukemia. These activation markers include CD3, CD8, CD56, CD16, and CD57. The NK form of LGL leukemia may show CD16+, CD56+, and CD3-. The T-cell form will usually show CD3+/CD8+ and CD57+.
The TCR test is usually done after a person has had the flow cytometry. This helps to narrow the field even further with regards to if there is a clone of the T-cell and if so, which type. There are two types of T-cell clones.
A bone marrow biopsy is another test that can show LGLs present. Flow cytometry tests can be run on the bone marrow as well as immunoperoxidase staining to show whether the markers employed in the flow cytometry are present.
In some cases of LGL leukemia, the patient may exhibit splenomegaly which is enlargement of the spleen. If this occurs the patient’s physician may consider performing a splenectomy (removal of the spleen). If the physician deems this necessary, subsequent analysis of the spleen may be done to see if there was an infiltration of LGLs. This is an invasive surgical procedure and should only be done after careful consideration by the physician and the patient.
Facts about T-cell LGL leukemia:
- T-cell LGL leukemia is a “chronic”, or slowly progressing, disease
- It usually occurs in people between the ages of 50 and 60
- About the same number of men and women get T-cell LGL leukemia
- About half of patients have anemia (less than normal amount of RBC)
- About half of patients have an enlarged spleen (splenomegaly)
- Bacterial infections are common and reoccur
- Rheumatoid arthritis is common
- Neutropenia (less than normal amount of neutrophils) is common
Facts about NK-cell LGL leukemia:
- NK-cell LGL leukemia has two forms: chronic and acute
Chronic form of NK-cell LGL leukemia:
- The clinical features of chronic NK LGL leukemia are very similar to those seen in T-LGL leukemia
- It is a chronic illness and is different than the acute form of NK LGL leukemia
- The chronic form does NOT change to the acute form
Acute form of NK-cell LGL leukemia:
- The acute form of NK-LGL leukemia is very rare
- There is a rapid increase in the number of LGLs over a few weeks’ time
- Unlike T-cell LGL leukemia, it can occur in a younger group of people
- About the same number of men and women get NK-cell LGL leukemia
- Systemic symptoms (such as fever and weight loss) are common
- Massive enlargement of the liver & spleen (hepatosplenomegaly) is common
- Most patients with the acute form die within two months of diagnosis
- Almost all patients have anemia (less than normal amount of red blood cells)
- Severe neutropenia (less than normal amount of neutrophils) is common