Diseases title

T-cell large granular lymphocyte leukemia )

Test molecule
Orpha Number: 86872
Synonym(s):
Proliferation of large granular lymphocytes, T-cell LGL leukemia, T-LGL

T-cell large granular lymphocyte leukemia (T-cell LGL leukemia) is a lymphoproliferative malignancy that arises from the mature T-cell (CD3+) lineage. It accounts for 2-5% of all chronic lymphoproliferative disorders in Western countries and the annual incidence has been estimated at 1 in 250,000. The median age at diagnosis is 60 years (male to female ratio 1:1). However, all age groups may be affected. T-cell LGL leukemia is characterized by neutropenia, anemia and/or thrombocytopenia, and moderate lymphocytosis. Approximately one third of patients are asymptomatic at the time of diagnosis. The initial symptoms are related to neutropenia and recurrent bacterial infections that typically involve the skin, oropharynx and perirectal areas. Sepsis or pneumonia may also occur, opportunistic infections are rare. Chronic fatigue is common. Fever, night sweats and weight loss are observed in 20-30% of cases. Moderate splenomegaly is frequent, while hepatomegaly and lymphadenopathy are rare. T-cell LGL leukemia is often associated with other diseases (autoimmune conditions in particular). The etiology is unknown. The causative role of chronic exogenous antigenic stimulation, retroviral infection and apoptotic inhibition is under investigation. The diagnosis is based on the presence of LGL lymphocytosis, a characteristic immunophenotype and confirmation of clonality using TCRbeta and gamma gene rearrangement studies. Differential diagnosis includes CD56+ cell proliferative diseases and those associated with reactive LGL proliferation (solid tumors, connective tissue diseases, hemophagocytosis syndrome, idiopathic thrombocytopenic purpura, non-Hodgkin's lymphoma (see this term) and viral infections). When T-cell LGL leukemia is associated with rheumatoid arthritis, it can be difficult to distinguish from Felty syndrome (rheumatoid arthritis, neutropenia, and splenomegaly; see this term). Immunosuppressive agents are used as a first-line therapy (methotrexate, cyclophosphamide, cyclosporine). Other treatments include chlorambucil, corticosteroids, deoxycoformycin, hematopoietic growth factors and alemtuzumab, with variable success. Prophylactic use of antibiotics can be beneficial. Careful observation should be offer to patients with indolent disease. Some patients remain asymptomatic for more than five years. Median survival extends to over ten years.
source: Orphanet