Abstract

Large granular lymphocytic (LGL) leukemia is a chronic lymphoproliferative disorder that exhibits an unexplained, chronic (> 6 months) elevation in large granular lymphocytes (LGLs) in the peripheral blood.

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

It is also known by the following terms: "proliferation of large granular lymphocytes" (LGLs), "LGL leukemia", "Tγ-lymphoproliferative disorder", and, in common with other T cell leukemias such as T-cell prolymphocytic leukemia, "T-cell chronic lymphocytic leukemia".

Signs and symptoms

This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.

Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.

Signs and symptoms | Sites of involvement

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

Cause

The postulated cells of origin of T-LGLL leukemia are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T-cell with clonal rearrangements of γ chain T-cell receptor genes for a minority of cases.

Diagnosis | Laboratory findings

The requisite lymphocytosis of this disease is typically 2-20x10/L.

Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen.

Diagnosis | 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 perforin and granzyme B.

Diagnosis | Bone marrow

Bone marrow involvement in this disease is often present, but to a variable extent. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs.

Diagnosis | Immunophenotype

The neoplastic cells of this disease display a mature T-cell immunophenotype, with the majority of cases showing a CD4-/CD8+ T-cell subset immunophenotype versus other permutations of those markers. Variable expression of CD11b, CD56, and CD57 are observed. Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive.

Diagnosis | Genetic findings

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.

Treatment

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

Prognosis

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

Epidemiology

T-LGLL is a rare form of leukemia, comprising 2-3% of all cases of chronic lymphoproliferative disorders.

History

LGLL was discovered in 1985 by Thomas P. Loughran Jr. while working at Fred Hutchinson Cancer Research Center. Specimens from patients with LGLL are banked at the University of Virginia for research purposes, the only bank for such purposes.