Large granular lymphocytic leukemia
Large granular lymphocytic leukemia is a rare form of chronic leukemia in which approximately 1,000 new cases are diagnosed each year in the United States. It was first introduced by Thomas Loughran Jr. in 1985 when abnormalities in large granular lymphocytes were found to be disrupting the body’s ability to maintain homeostasis within blood cells.
Definition & Facts
Lymphocytes (also known as white blood cells) are an important part of the body’s immune system. They are responsible for fighting certain infections such as bacterial infections. Large granular lymphocytic leukemia affects these white blood cells, causing them to become very enlarged and contain large pink granules, visible in blood under a microscope.
While in many cases the problem arises when the proliferation of these cells is so high that they outnumber other types of cells necessary within the blood such as red blood cells, plasma, and especially neutrophils, in most cases the culprit is the lymphocytes are so enlarged that the proportion between them and other blood components is vastly out of balance.
These abnormal cells multiply themselves and spread throughout the body. This may be a slow and chronic process, or it may be more aggressive and fast moving. This adversely affects the body’s ability to fight infection and reproduce red blood cells.
LGL leukemia affects both men and women equally and generally presents itself around a median age of 60, with only 20-25% of patients being diagnosed under the age of 50. LGL leukemia is classified into types depending on which type of lymphocytes are involved: T-Cell LGL leukemia and natural killer cell, or NK-cell LGL leukemia.
Symptoms & Complaints
- Chronic weakness
- Ongoing abnormalities indicated in complete blood counts, particularly that of visibly enlarged lymphocytes containing large pink granules, the hallmark of LGL leukemia.
- Decreased production of red blood cells known as pure red cell aplasia.
- Chronic neutropenia, the low concentration of the white blood cells known as neutrophils within the blood.
- Frequent infections and fevers.
- Night sweats
- Unexplained weight loss
- 25-50% have an enlarged spleen (splenomegaly).
- Rare cases have an enlarged liver (hepatomegaly) and/or swollen lymph nodes.
There is no known specific cause of large granular lymphocytic leukemia. One common factor among cases that indicate a possible predisposition to this disease is the presence of anti-nuclear antibodies and rheumatoid factors in the blood.
In up to 25% of cases, patients were previously diagnosed with autoimmune diseases, which were diagnosed by the presence of these factors. The most common autoimmune diseases present in LGL leukemia patients are rheumatoid arthritis, Sjögren's syndrome, Hashimoto’s thyroiditis, and lupus. The common presence of these factors indicates that chronic overactivity within the immune system may play a part in the genetic mutation and proliferation of these abnormal white blood cells.
As with other forms of cancer, LGL leukemia is not contagious and cannot be passed from one person to another. Studies have also shown that the disease is not hereditary, though genetic testing has shown many patients exhibit abnormalities in the gene known as STAT3, leading to a hypothesis that this may be a cause for LGL leukemia, however, further studies are being conducted to determine its accuracy.
Diagnosis & Tests
A physician will start with a complete medical history and physical examination to assess any symptoms and complaints the patient is having. Routine laboratory blood tests will be performed and if abnormalities such as a low concentration of neutrophils (neutropenia), decreased red blood cells, or the hallmark LGL leukemia indicator of a disproportionate enlarged LGL’s are present, further testing will be required.
A bone marrow biopsy may be performed. This sample of fluid and solid tissue from the bone marrow will allow the doctor to look for abnormalities and is done under local anesthesia. Another diagnostic tool that will be used if LGL leukemia is detected is a flow cytometry test. This is a specialized procedure that helps determine if the LGL leukemia cells are T-Cells or natural killer cells (NK-cells) by separating each component of blood or bone marrow and counting it.
X-rays and imaging tests such as ultrasounds or computed tomography (CT) scans are used to examine organs for abnormalities caused by LGL leukemia. In rare cases in which the patient presents with an enlarged spleen, a splenectomy may be performed for a spleen analysis.
Treatment & Therapy
The course of treatment will depend on the severity of each case. Patients with severe neutropenia and/or anemia will require treatment to begin immediately, while patients with a lower severity may start with a "watch and wait" approach. There is no one-size-fits-all course of treatment; consideration is taken on a case by case basis.
Many patients may decide with their doctor to take part in an available clinical trial that is well suited for their particular case. Initial treatments commonly include medications such as methotrexate, an immunosuppressive drugs, oral cyclophosphamide or ciclosporine, or an immunomodulatory drug.
In more aggressive or severe cases, chemotherapy is often utilized and/or the spleen may be removed. While there is no cure for LGL leukemia, the most successful approach to a severe case is a stem cell or bone marrow transplant. This is performed ideally using a closely matched and healthy sibling’s donor bone marrow to replace the damaged bone marrow in the LGL leukemia patient.
Treatment using medications is generally continued for approximately four months and testing is repeated to see if the patient is having a positive response to therapy. If the patient is responding well, maintenance therapy may be done using methotrexate or cyclosporine indefinitely.
Prevention & Prophylaxis