Clinical features of large granular lymphocyte leukemia

Semin Hematol. 2003 Jul;40(3):185-95. doi: 10.1016/s0037-1963(03)00133-1.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Autoimmune Diseases
  • Clone Cells / immunology
  • Clone Cells / pathology
  • Hematologic Diseases
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Leukemia, Lymphoid / complications
  • Leukemia, Lymphoid / etiology
  • Leukemia, Lymphoid / pathology*
  • Leukemia, Lymphoid / therapy
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology