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T-cell large granular lymphocyte leukemia is a chronic clonal lymphoproliferation of cytotoxic T cells often associated with immune-mediated cytopenias. The pathophysiology of cytopenias includes cytokine effects and direct antigen-specific cytotoxicity to hematopoietic precursors. This review will address the diagnostic challenges of and therapeutic options for T-cell large granular lymphocyte leukemia.Immunosuppressive therapy, with cyclosporine, methotrexate, and oral cyclophosphamide, is often used, but formal trials have not been performed and response rates are poorly established. In refractory cases, alternative regimens such as antithymocyte globulin or monoclonal antibody therapy have exhibited hematologic response.T-cell large granular lymphocyte leukemia may assume an indolent course but sometimes manifests with significant cytopenias. A majority of patients will ultimately require immunosuppressive therapy due to symptomatic neutropenia or anemia. In these cases, a variety of agents maybe used successfully though chronic therapy is often necessary.