Chapter 12 - T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis

Abstract

T-cell large granular lymphocytic (T-LGL) leukemia is a rare type of indolent T-cell neoplasm. The typical features of T-LGL leukemia include cytopenia (most commonly neutropenia), an increased number of large granular lymphocytes (LGLs) in the peripheral blood, and moderate splenomegaly. Up to 28% of patients with T-LGL leukemia are diagnosed with rheumatoid arthritis (RA), while clonal expansion of LGLs has been detected in 3.6% of patients with RA. T-LGL leukemia is usually diagnosed 10–20 years after the manifestation of RA; however, both conditions may present simultaneously, or T-LGL leukemia may even precede the clinical manifestations of RA by several years. Activating somatic mutations of the signal transducer and activator of transcription 3 (STAT3) gene are identified in 27%–72% of T-LGL leukemia cases. These patients are more prone to developing RA than patients without mutations. Notably, the clinical features of T-LGL leukemia in the RA setting may mimic Felty’s syndrome. In this chapter, the epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and treatment options for RA-associated T-LGL leukemia are discussed.