Treatment of large granular lymphocyte leukemia
- Thierry Lamy, MD, PhD
Thierry Lamy, MD, PhD
- Professor in Hematology
- University of Rennes, France
- Thomas P Loughran, Jr, MD
Thomas P Loughran, Jr, MD
- Director, University of Virginia Cancer Center
- University of Virginia
Large granular lymphocyte (LGL) leukemia is characterized by peripheral blood and marrow lymphocytic infiltration with clonal LGLs, splenomegaly, and cytopenias, most commonly neutropenia.
The LGL is a morphologically distinct lymphoid subset that is larger than most circulating lymphocytes, and has characteristic azurophilic granules containing acid hydrolases (picture 1). LGLs comprise 10 to 15 percent of normal peripheral blood mononuclear cells. The absolute number of LGLs in the peripheral blood of normal subjects is 200 to 400/microL.
LGLs arise from two major lineages [1,2]. About 85 percent of normal LGLs have an NK cell phenotype, and only 15 percent are derived from T cells. The phenotypes of LGLs in LGL leukemia, however, are just the opposite:
●CD3 positive T cell lineage — Approximately 85 percent of circulating LGLs are CD3 positive, CD57 positive, CD56 negative T cells, representing in vivo antigen-activated effector-memory cytotoxic T cells.
●CD3 negative NK cell lineage — The remaining 15 percent of circulating LGLs are CD3-, CD56+ natural killer (NK) cells. It had been postulated that such NK cells mediate non-major histocompatibility complex (MHC)-restricted cytotoxicity. It is now established that NK cells possess specific receptors for MHC class I molecules named "killer-cell Ig-like inhibitory receptor" (KIR) and "killer-cell activating receptor" (KAR). Interactions between these receptors and MHC class I molecules on target cells may inhibit or activate NK cell–mediated cytotoxicity.
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- INDICATIONS FOR TREATMENT
- MANAGEMENT OF ASYMPTOMATIC PATIENTS
- PRETREATMENT EVALUATION
- INITIAL TREATMENT
- Choice of therapy
- RESPONSE EVALUATION
- TREATMENT OF RELAPSED OR RESISTANT DISEASE
- Relapsed disease
- Resistant disease
- Refractory or aggressive disease
- - Alemtuzumab
- - Purine analogs
- - Splenectomy
- - Other therapies
- CLINICAL TRIALS
- SUMMARY AND RECOMMENDATIONS