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The Oncologist, Vol. 11, No. 3, 263-273, March 2006; doi:10.1634/theoncologist.11-3-263
© 2006 AlphaMed Press

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Large Granular Lymphocyte Leukemia

Lubomir Sokola, Thomas P. Loughran, Jr.b

a Department of Interdisciplinary Oncology, University of South Florida and H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA; b Penn State Cancer Institute, Penn State College of Medicine, Hershey, Pennsylvania, USA

Key Words. T-cell LGL leukemia • Aggressive NK-cell leukemia • Cytopenia • Autoimmunity

Correspondence: Thomas P. Loughran, Jr., M.D., Penn State Cancer Institute, Penn State College of Medicine, 500 University Drive, H072, Hershey, Pennsylvania 17033, USA; Telephone: 717-531-7096; Fax: 717-531-0778; e-mail: tloughran{at}psu.edu

Clonal disorders of large granular lymphocytes (LGLs) represent a spectrum of biologically distinct lymphoproliferative diseases originating either from mature T cells (CD3+) or natural killer (NK) cells (CD3–). Both subtypes, T-cell and NK-cell LGL leukemia, can manifest as indolent or aggressive disorders. The majority of patients with T-cell LGL leukemia have a clinically indolent course with a median survival time >10 years. Immunosuppressive therapy with low-dose methotrexate, cyclophosphamide, or cyclosporine A can control symptoms and cytopenias in more than 50% of patients, but this approach is not curative. Several cases of an aggressive variant (CD3+CD56+) of T-cell LGL leukemia with a poor prognosis have also been reported. Aggressive NK-cell LGL leukemia is usually a rapidly progressive disorder associated with Epstein-Barr virus (EBV), with a higher prevalence in Asia and South America. This disease is usually refractory to conventional chemotherapy, with a median survival time of 2 months. Chronic NK-cell leukemia/lymphocytosis is a rare EBV-negative disorder with an indolent clinical course. The malignant origin of this subtype is uncertain because clonality is difficult to determine in LGLs of NK-cell origin.




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