Large granular lymphocyte leukemia. Report of 38 cases and review of the literature.

LGL leukemia results from a chronic, clonal proliferation of LGL. Chronic neutropenia with recurrent bacterial infection and splenomegaly are common clinical manifestations. Rheumatoid arthritis coexists in some of these patients, who thus resemble patients with Felty syndrome. Other hematologic abnormalities that may occur include pure red-cell aplasia and adult-onset cyclic neutropenia. Lymphoid infiltration of bone marrow, splenic red pulp cords, and hepatic sinusoids is characteristic; lymph node and skin involvement are rare. Multiple serologic abnormalities are frequently present, including positive tests for rheumatoid factor and/or antinuclear antibody, polyclonal hypergammaglobulinemia, and circulating immune complexes. Antineutrophil and antiplatelet antibodies are often present. Leukemic LGL exhibit phenotypic heterogeneity; the most common phenotype in our patients is CD2+, CD3+, CD8+, HNK-1+, CD16-. Despite markedly increased numbers of LGL, functional activity of the cells is usually decreased. The mechanism of cytopenias is uncertain: in pure red-cell aplasia, it appears to be due to suppressive effect on erythropoiesis by abnormal LGL, but in patients with chronic neutropenia it may be antibody-mediated. Although most patients appear to have a relatively benign clinical course, mortality from infections and progressive lymphoproliferation is substantial. Optimal therapy remains undefined. Some preliminary evidence suggests that LGL leukemia may be associated with infection with a retrovirus similar to HTLV-I. Although relatively rare, LGL leukemia is of interest because a better understanding of this disease process may contribute to our knowledge of autoimmune diseases, the immunoregulatory functions of LGL, and the mechanisms controlling normal hematopoiesis.