Large Granular Lymphocytic Leukemia: Current State of Diagnosis, Pathogenesis and Treatment

This manuscript aims at updating the knowledge on the clinico-biological characteristics, pathogenesis, and the diagnostic challenges of T-LGLL and CLPD-NK disorders and reviews the advances in the management and treatment of these patients.

It has been shown that clonal large granular lymphocyte (LGL) expansions arise from chronic antigenic stimulation, leading to resistance to apoptosis. All the above findings have facilitated the diagnosis of LGLL and provided insights in the pathogenesis of the disease. At present, there is no standard first-line therapy for the disease. Immunosuppressive agents are the treatment routinely used in clinical practice. However, these agents have a limited capacity to eradicate the LGL clone and induce long-lasting remission. Advances in the knowledge of pathogenesis have made it possible to explore new therapeutic targets with promising results. Since LGLL is a rare disease, international efforts are needed to carry on prospective clinical trials with new potentially active drugs that could include a large number of patients.