Large Granular Lymphocytic Leukemia - Natural Killer Cell Leukemia

Introduction:

Large granular lymphocytic leukemia is a rare type of chronic leukemia that mainly affects the lymphocytes (white blood cells). These lymphocytes are defensive cells of the body that fight against infection, viruses, and bacteria. Leukemia is a blood cancer in the bone marrow's immature blood-forming cells (hematopoietic precursor cells). Leukemia is the most common cancer in children. There is an increased risk of infection and anemia in these patients because of a deficiency of white blood cells.

What Is the Pathogenesis of Large Granular Lymphocytic Leukemia?

The blood cells are produced from the bone marrow located inside the bone. It comprises blood-forming cells, supporting tissues, and fat cells. These blood-forming cells multiply to form.

• Red blood cells (RBCs).

• White blood cells (WBCs).

• Platelets.

The white blood cells help fight infections in the body. The types of WBC are Lymphocytes, granulocytes, and monocytes.

• Lymphocytes develop from lymphoblasts to become mature, infection-fighting cells.

• The red bone marrow is the active bone marrow that produces blood cells. The red bone marrow is found in large bones such as the breast bone, vertebrae, skull, pelvis, and ribs, and the ends of long bones such as the humerus and femur.

• The yellow bone marrow contains only fat cells. If there are more blood cell requirements, then the yellow bone marrow gets activated and changes into blood cells producing red bone marrow.

• The hematopoietic precursor cells are of two types: lymphoid cells and myeloid cells. The lymphoid cells produce T and B-lymphocytes and natural killer cells. The myeloid cells produce red blood cells, and white blood cells- basophils, eosinophils, neutrophils, monocytes, mast cells (except for B and T-lymphocytes), and platelets.

• It is called lymphoblastic or lymphocytic leukemia if the cancerous change occurs in lymphoid cells such as T-cells, B-cells, or natural killer cells.

• It is called myeloid leukemia if the cancerous change occurs in red blood cells, other white cells, and platelets.

What Are the Types and Causes of Large Granular Lymphocytic Leukemia (LGL)?

The two types of large granular lymphocytic leukemia are a chronic lymphoproliferative disorder of natural killer cells and T-cell large granular lymphocytic leukemia. The condition develops either from natural killer cells or cytotoxic T-cells. Large granular lymphocytic leukemia occurs when the natural killer cells and T-lymphocytes become abnormal or undergo changes and prevent the bone marrow from producing normal blood cells. The types are:

• T-cell granular lymphocytic leukemia.

• Aggressive NL-cell leukemia.

• Chronic lymphoproliferative disorder of natural killer cells.

In almost all cases, the reason is unknown. Several factors are associated with leukemia, including:

• Cytotoxic therapy for breast, lung, and testicular cancer.

• Chronic exposure to certain chemicals, such as benzene and alkylating drugs.

• The previous history of treatment with ionizing radiation.

• A defect in the genetic programming of the precursor cells.

• Family history of leukemia (1st degree relatives of patients have a three times greater chance of having leukemia).

• Viruses include Human T-cell leukemia/lymphoma (HTLV-1) and HIV (Human immunodeficiency virus).

• Smoking.

• Many people carry mutated genes of STAT3 and STAT5B that play a crucial role in cell immunity and cell multiplication.

What Are the Symptoms of Large Granular Lymphocytic Leukemia?

Autoimmune diseases like rheumatoid arthritis (inflammation of the joints) are associated with large granular lymphocytic leukemia. The other conditions that are linked to this type of leukemia are:

1. Neutropenia - In this condition, there are low levels of neutrophils, and it is common among people receiving cancer treatments. The neutrophils help fight infections, and when the count is very few, people are prone to many infections.

2. Hemolytic Anemia - It is a blood disorder that happens when the red blood cells break down faster and the body cannot replace them at the rate of breakdown. Red blood cells normally survive for 120 days. In hemolytic anemia, the bone marrow does not produce new red blood cells.

The affected individuals usually do not show any symptoms. Only the blood tests show low levels of neutrophils (granulocytes) or red blood cells. The following are some of the symptoms:

• Infections and recurrent fever caused by bacterial infections.

• Splenomegaly (enlarged spleen) is caused by anemia and infections.

• Fatigue (extreme tiredness) because of anemia.

• Red cell aplasia (decline in red blood cell count).

• The decline in the number of red blood cells (anemia).

• Weight loss.

• Enlargement of the spleen (splenomegaly).

• Enlargement of the liver (hepatomegaly).

• Lymphadenopathy (swollen lymph nodes).

• Recurrent infections.

What Is the Diagnosis of Large Granular Lymphocytic Leukemia?

The following diagnosis are done:

• Peripheral Blood Smear - The blood cells are examined under the microscope for large cells.

• Flow Cytometry - It is a laser-based technique that detects cells' physical and chemical characteristics. It evaluates the body's peripheral blood, bone marrow, and fluids. A sample of cells is injected into a flow cytometer for cell counting, sorting, determining cell functions and characteristics, detecting the micro-organisms, and finding biomarkers.

• Immunophenotyping - In this type of testing, the specific markers or antigens on the cells are identified. The process uses antibodies based on the type of markers on the surface of the cells to kill them.

• Genetic Testing - The genes STAT3 and STAT5 genes are tested for mutations.

What Is the Treatment for Large Granular Lymphocytic Leukemia?

Initially, wait and watch therapy is done. Most of the treatments include a combination of immune-suppressing drug therapy and chemotherapy. The initial medications includes:

• Immunosuppressive therapy includes Methotrexate.

• Oral alkylating agents such as Cyclophosphamide. Cyclophosphamide therapy is given for 5 to 12 months.

• Purine analogs like Fludarabine with Dexamethasone.

• In some splenomegaly patients, surgical removal of the spleen is done (splenectomy).

• CHOP is a combination of chemotherapy. The drugs used in chemotherapy are Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

Conclusion:

The main drugs used for treatment are low-dose Methotrexate, Cyclophosphamide, Vincristine, and Prednisone. If the cancer is detected early, it is easier to treat. The treatments of leukemias are based on the stage of the diagnosis. Treatment involves chemotherapy, radiation therapy, stem cell transplant, surgery, and targeted therapy with monoclonal antibodies. Survival chances are more if the disease is diagnosed and treated at the early stage itself.