Diagnosis and Management of Large Granular Lymphocytic Leukaemia and Its Differentiation From T Cell Clones of Uncertain Significance.

Large granular lymphocytic leukemia (LGLL) is a chronic clonal T- or NK-cell disorder that can cause significant cytopenias. Different phenotypes and genotypes have been associated with different clinical courses. LGLL can be associated with numerous other conditions including infections, other malignancies and autoimmune disease. When symptomatic, the mainstay of treatment is immunosuppression. However, time to response can be slow and response rates and durability of response can be disappointing. With improved understanding of the pathogenesis of the disease, new treatments such as JAK inhibitors are showing promise. Increasingly, T-cell clones that do not fulfill the diagnostic criteria for large granular lymphocytic leukemia are being identified, and these can provide diagnostic complexity, especially if associated with cytopenias. Many of these clones have a similar immunophenotype to LGLL. In these cases, bone marrow investigations can be helpful to differentiate between a "low-count" LGLL and T cell clone of uncertain significance (TCUS). Little is known about the natural history of TCUS at present, and so it is advised to monitor patients in a similar fashion as those with monoclonal B lymphocytosis.