Large Granular Lymphocytic Leukemia

Large granular lymphocytic (LGL) leukemia is a type of chronic leukemia affecting white blood cells called "lymphocytes."  Lymphocytes are part of the body's immune system and help fight certain infections. LGL leukemia is characterized by enlarged lymphocytes, containing noticeable granules, which can be seen when the blood is examined under the microscope. There are two types of LGL leukemia: T-cell (T-LGL) and natural killer cell (NK-LGL). Each type may be chronic (slow-growing) or aggressive (fast-growing). 

The frequency of T-cell and NK-cell LGL leukemia ranges from 2 to 5 percent of chronic lymphoproliferative diseases. LGL leukemia affects both men and women, and the median age at diagnosis is 60 years.  Less than a quarter of patients are younger than 50 years.

Chronic T-cell and NK-cell LGL Leukemia

Signs and Symptoms

The majority of 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)
  • Below-normal concentration of neutrophils, a type of white cell (chronic neutropenia)
  • Decrease in the number of red cells (anemia) occurs in about half of patients
  • Recurrent infections
  • Fever
  • Night sweats
  • Unintended weight loss
  • Enlargement of the spleen (splenomegaly) occurs in 25 to 50 percent of patients
  • Enlargement of the liver (hepatomegaly) rarely occurs
  • Swollen lymph nodes (lymphadenopathy) rarely occurs.

Risk Factors

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

Diagnosis

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. 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.

Treatment

Chronic T-cell and NK-cell LGL leukemia patients require similar treatment. For some patients, a watch and wait approach may be considered; however, the 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 auto-immune 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 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 he or she has 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, he or she 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) 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®)
  • In some patients, splenectomy

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

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 is 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 prophylaxis (CNS), 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., M.D.

Related Links

  • Click here to find out more about the LGL Leukemia Registry.
  • Click here to learn more about other disease registries.

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