Clinical features of large granular lymphocyte leukemia.
The spectrum of large granular lymphocyte (LGL) proliferations consists of four distinct entities: reactive/transient LGL expansion, chronic LGL lymphocytosis, classical indolent LGL leukemia, and aggressive LGL leukemia. LGL leukemias are classified as lymphoid malignancies. They are divided into CD3(+)/T-cell LGL (85% of cases) and CD3(-)/natural killer (NK) cell LGL leukemia (15% of cases). Recent progress in the comprehension of the leukemogenesis has shown a dysregulation of survival signals in leukemic cells. Identification of LGL expansion has been improved using T-cell receptor (TCR)beta/gamma polymerase chain reaction (PCR) analysis and a combination of Vbeta and killer cell immunoglobulin-like receptor (KIR)-specific monoclonal antibodies. LGL leukemias are characterized by a clonal LGL infiltration of the bone marrow, spleen, and liver. Monoclonality is recognized by phenotypic, molecular, and karyotypic analysis. T-LGL leukemias affect the elderly and display a relatively indolent behavior. Approximately 60% to 70% of patients are symptomatic: recurrent infections secondary to chronic neutropenia, anemia, and autoimmune disease such as rheumatoid arthritis are the main clinical manifestations. Long-lasting remission can be obtained with low-dose methotrexate, cyclosporine A, or cyclophosphamide. Conversely, NK LGL leukemias behave aggressively, and most patients do not respond to chemotherapy.
Lamy
Thierry
T
Department of Hematology, Pontchaillou University Hospital, Rennes, France.
Loughran
Thomas P
TP
D001327:Autoimmune Diseases; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D006402:Hematologic Diseases; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D007945:Leukemia, Lymphoid / Q000150:complications / Q000209:etiology / Q000473:pathology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology