T-Cell Large Granular Lymphocyte Leukemia and Related Disorders

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Discuss the clinical manifestations of large granular lymphocyte leukemia and related disorders, including their association with autoimmune conditions. Describe recent developments in the understanding of the pathogenesis of large granular lymphocyte leukemia. Explain the treatment approach to large granular lymphocyte leukemia and its related disorders. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at http://CME.TheOncologist.com T-cell large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic T cells, which causes neutropenia, anemia, and/or thrombocytopenia. This condition is often associated with autoimmune disorders, especially rheumatoid arthritis, and other lymphoproliferative disorders. The diagnosis is suggested by flow cytometry demonstrating an expansion of CD8+CD57+ T cells and is confirmed by T-cell receptor gene rearrangement studies. Mounting evidence suggests that LGL leukemia is a disorder of dysregulation of apoptosis through abnormalities in the Fas/Fas ligand pathway. In most patients, this is an indolent disorder, and significant improvement of cytopenias can be achieved with immunosuppressive agents such as steroids, methotrexate, cyclophosphamide, and cyclosporin A. This review provides a concise, up-to-date summary of LGL leukemia and the related, more aggressive, malignancies of cytotoxic T cells and natural killer cells.