TY - CHAP M1 - Book, Section TI - Large Granular Lymphocytic Leukemia A1 - Brammer, Jonathan E. A1 - Mishra, Anjali A1 - Freud, Aharon G. A1 - Porcu, Pierluigi A2 - Kaushansky, Kenneth A2 - Prchal, Josef T. A2 - Burns, Linda J. A2 - Lichtman, Marshall A. A2 - Levi, Marcel A2 - Linch, David C. PY - 2021 T2 - Williams Hematology, 10e 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 2016 World Health Organization entity, chronic lymphoproliferative disorders of NK cells (CLPD-NK), are similarly defined as persistent (>6 months) and clonal expansions in blood LGLs, often without a clearly identifiable cause. These patients 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 LGL leukemia 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 T-LGLL patients 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, 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, alemtuzumab, and more recently peptides that inhibit inflammatory cytokines such as interleukin-15. Prospective studies are ongoing to define the respective role of these agents in LGLL. SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/11/08 UR - hemonc.mhmedical.com/content.aspx?aid=1178750718 ER -