T cell large granular lymphocyte leukemia associated with rheumatoid arthritis and neutropenia.

T cell large granular lymphocyte leukemia (T-LGL) is a disease characterized by clonal expansion of cytotoxic T cells (CTLs). It generally follows an indolent course and is notable for an association with chronic inflammation, neutropenia and rheumatoid arthritis (RA). We present herein a case of a patient with rheumatoid arthritis (RA), neutropenia, large granular lymphocytosis, and an expanded clonal population of peripheral blood CD3(+)CD8(+)TCRalphabeta CTLs, consistent with the diagnosis of T-LGL. T-LGL is part of a spectrum of large granular lymphocytic (LGL) disorders, which includes the more common indolent variety of this disease (as illustrated by the case herein), an aggressive but rare form of this leukemia, natural killer (NK) cell LGL leukemia, Felty's syndrome (FS), and chronic large granular lymphocytosis. T-LGL appears to be a relatively rare disease, but the true prevalence is not known. FS occurs in less than 1% of patients with RA and is typically defined by the triad of destructive arthritis, neutropenia, and variable splenomegaly. A subset of patients with FS will demonstrate polyclonal expansion of LGLs, implying a relationship between proliferation of LGLs and the mechanisms of neutropenia. Thus, T-LGL leukemia and FS with LGL expansion in the setting of RA is classically distinguished by the clonality of the CTL population, with monoclonality in T-LGL and polyclonality in FS. Despite this difference, T-LGL and FS are often similar in their clinical and biological behavior. Both may respond to immunosuppressive therapy, and pursue a smoldering course typical of a chronic inflammatory disease.

Duke Scholars

Author Ankoor Shah Medicine, Rheumatology and Immunology

Author Louis Frederic Diehl Medicine, Hematologic Malignancies and Cellular Therapy

Author Eugene William St. Clair Medicine, Rheumatology and Immunology