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 2-20x109/L.Immunoglobulin derangements including hypergammaglobulinemia, autoantibodies, and circulating immune complexes are commonly seen. 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. Flow cytometry is also commonly used. Bone marrow
Bone marrow involvement in this disease is often present, but to a variable extent. Bone marrow biopsy is commonly used for diagnosis. The lymphocytic infiltrate is usually interstitial, but a nodular pattern rarely occurs. 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. 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.Current evidence suggests that patients with STAT3 mutations are more likely to respond to methotrexate therapy. Treatment
First line treatment is immunosuppressive therapy.
A weekly dosage of Methotrexate (with or without daily Prednisone) may induce partial or complete response in some patients while others may require Cyclosporine or Cyclophosphamide.Alemtuzumab has been investigated for use in treatment of refractory T-cell large granular lymphocytic leukemia.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. 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. References


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