Large granular lymphocytic (LGL) leukemia

 What are signs and symptoms of LGL?

Most patients diagnosed with chronic T-cell and NK-cell LGL leukemia have symptoms at the time of diagnosis.  

The following signs and symptoms may be present: 

• Changes in blood cell counts
• Decline in the production of red blood cells (red cell aplasia)
• Chronic “neutropenia,” below-normal concentration of neutrophils, a type of white cell
• “Anemia,” a decrease in the number of red cells, occurring in about half of patients
• Recurrent infections
• Fever
• Night sweats
• Unintended weight loss
• Enlargement of the spleen (splenomegaly), occurring in 25 percent to 50 percent of patients
• Enlargement of the liver (hepatomegaly), occurring rarely
• Swollen lymph nodes (lymphadenopathy), occurring rarely 

What are risk factors for LGL?

Autoimmune diseases (such as rheumatoid arthritis) are diagnosed before the onset of LGL leukemia in about 20 percent of cases.

How is LGL diagnosed? 

To help confirm a diagnosis, your doctor may examine your blood under a microscope. The lymphocyte count may be normal or low (and lymph nodes are not typically enlarged). Patients may have a large number of abnormal cells associated with LGL leukemia. A bone marrow aspiration or biopsy might be necessary to confirm the diagnosis. Flow cytometry can determine if the LGL leukemia cells are T-cells or NK cells. 

Learn more about lab and imaging tests. 

How is LGL treated?

Chronic T-cell and NK-cell LGL leukemia patients require similar treatment. For some patients, a watch-and-wait approach may be considered; however, a majority of patients will eventually require treatment. For patients on watch and wait, indications to begin treatment include moderate to severe neutropenia, symptomatic or transfusion-dependent anemia, and associated autoimmune conditions (such as rheumatoid arthritis) requiring therapy. 

There is no one standard treatment for chronic LGL leukemia, so patients are advised to speak to their doctors about the possibility of treatment in a clinical trial.  

Therapies that have been shown to be the most beneficial for initial treatment include: 

• Immunosuppressive therapy, such as methotrexate
• Oral cyclophosphamide, an alkylating agent
• Cyclosporine, an immunomodulatory drug 

Patients may receive drug therapy for about four months before tests are done to see if the therapy is working. At this point, a patient should be tested to see if they have achieved a complete hematologic response or a partial hematologic response. Another test that may be used is polymerase chain reaction (PCR) to detect a concentration of residual LGL cells too low to be seen using a microscope. If a patient is responding to therapy and the disease is under control, they can continue taking methotrexate and/or cyclosporine indefinitely. Cyclophosphamide therapy given for 4 to 12 months, because of toxicity, is not an ongoing treatment. If a patient does not reach these goals, a different treatment should be started.  

Other treatments include the following: 

• Purine analogs, such as fludarabine with mitoxantrone and dexamethasone
• Splenectomy (surgical removal of the spleen), which has shown limited results 

Patients whose disease has relapsed can resume initial treatment or opt for another immunosuppressive treatment. Patients whose disease is refractory (has not responded to treatment) can be treated with: 

• Purine analogs
• Alemtuzumab (Campath®)
• Splenectomy, in some patients 

Periodic examinations, complete blood counts (CBCs), and polymerase chain reaction (PCR) are used to monitor patients in remission. 

For information about the drugs listed on this page, visit our cancer drug listing. 

Aggressive T-cell and NK-cell LGL leukemia 

Patients who have aggressive T-cell or NK-cell LGL leukemia may have enlargement of the liver and spleen (hepatosplenomegaly), fever, unintended weight loss, and night sweats. 

Unfortunately, aggressive T-cell and NK-cell LGL leukemia are resistant to therapy. There is limited data about which therapies work best with these aggressive diseases; however, therapies similar to those used to treat acute lymphoblastic leukemia (ALL) are used. Induction chemotherapy including central nervous system (CNS) prophylaxis, followed by consolidation and stem cell transplantation at the time of first remission, may be an option and provide a better outcome. A clinical trial may be the best available treatment. 

Reviewed by Thomas P. Loughran, Jr., MD.

Related links 

• Find out more about the LGL Leukemia Registry.
• Learn more about other disease registries.