Large granular lymphocytic leukemia

Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular

It is divided in two main categories: T-cell LGL leukemia (T-LGLL) and natural-killer (NK)-cell LGL leukemia (NK-LGLL). As the name suggests, T-cell large granular lymphocyte leukemia is characterized by involvement of cytotoxic-T cells).^[2]

In a study based in the US, the average age of diagnosis was 66.5 years^[3] whereas in a French study the median age at diagnosis was 59 years (with an age range of 12–87 years old).^[4] In the French study, only 26% of patients were younger than 50 years which suggests that this disorder is associated with older age at diagnosis.^[4] Due to lack of presenting symptoms, the disorder is likely to be underdiagnosed in the general population.^[5]

Signs and symptoms

This disease is known for an indolent clinical course and incidental discovery.

The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.^[1][7]

Cause

The postulated cells of origin of T-LGLL leukemia are transformed CD8+

The requisite lymphocytosis of this disease is typically 2-20x10⁹/L.^[12]

Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.^{[10][13][14][15]}

Peripheral blood

The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in cell lysis such as

Clonal rearrangements of the T-cell receptor (TCR) genes are a necessary condition for the diagnosis of this disease. The gene for the β chain of the TCR is found to be rearranged more often than the γ chain. of the TCR.^[14][18]

Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy.^[19]

Treatment

First line treatment is immunosuppressive therapy. A weekly dosage of

Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.^[20]

Experimental data suggests that treatment with calcitrol (the active form of vitamin D) may be useful in treating T-cell LGL due to its ability to decrease pro-inflammatory cytokines.^[21]

Prognosis

The 5 year survival has been noted as 89% in at least one study from France of 201 patients with T-LGL leukemia.^[4]

Epidemiology

T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.^{[citation needed]}

History

LGLL was discovered in 1985 by