RT Book, Section A1 Porcu, Pierluigi A1 Freud, Aharon G. A2 Press, Oliver W. A2 Lichtman, Marshall A. A2 Leonard, John P. SR Print(0) ID 1148368071 T1 Large Granular Lymphocytic Leukemia T2 Williams Hematology Malignant Lymphoid Diseases YR 2017 FD 2017 PB McGraw-Hill Education PP New York, NY SN 9781260117066 LK hemonc.mhmedical.com/content.aspx?aid=1148368071 RD 2024/03/28 AB SUMMARYIndolent clonal proliferations of large granular lymphocytes (LGLs) can arise from either T cells or natural killer (NK) cells. These diseases show overlapping clinical, morphologic, immunophenotypic, and genetic features. T-cell large granular lymphocytic leukemia (T-LGLL) and the related provisional 2008 World Health Organization entity chronic lymphoproliferative disorders of NK cells (CLPD-NK) are similarly defined as persistent (>6 months) and with clonal expansions in blood LGLs, often without a clearly identifiable cause. Patients with these diseases are typically older, present with single-lineage or multilineage cytopenias, and often have clinical and laboratory features of autoimmunity or immune dysfunction. Autoimmune neutropenia, thrombocytopenia, hemolytic anemia, and occasionally pure red cell aplasia may occur. Patients with T-LGLL frequently have elevated rheumatoid factor and clinical hallmarks of rheumatoid arthritis. The diagnosis of LGLL requires a high degree of suspicion and careful examination of the blood film because a significant fraction of patients do not have an absolute lymphocytosis, although the proportion of LGLs is usually increased. Most patients with T-LGLL and fewer with CLPD-NK have chronic neutropenia, and approximately half of patients with T-LGLL have neutrophil counts less than 0.5 × 109/L. Anemia is observed in approximately half of patients with T-LGLL. Morbidity and mortality usually result from recurrent infections secondary to chronic neutropenia or transfusion-related iron overload and less frequently from disease acceleration and transformation into a more aggressive T/NK leukemia or lymphoma. The treatment approach generally consists of immune-modulatory or immune-suppressive drugs, such as weekly oral methotrexate, cyclophosphamide, cyclosporine, prednisone, and alemtuzumab. Prospective studies are examining the role of these agents in LGLL.