Advances in diagnosis and treatment of large granular lymphocyte syndrome

Large granular lymphocyte (LGL) syndrome comprises a clonal spectrum of T-cell and natural killer (NK)-cell LGL lymphoproliferative disorders associated with neutropenia. This review presents advances in diagnosis and therapy of LGL syndrome.

Due to the lack of a single unique genetic or phenotypic feature and clinicopathological overlap between reactive and neoplastic entities, accurate LGL syndrome diagnosis should be based on the combination of morphologic, immunophenotypic, and molecular studies as well as clinical features. For diagnosis and monitoring of LGL proliferations, it is essential to perform flow cytometric blood and/or bone marrow analysis using a panel of monoclonal antibodies to conventional and novel T-cell and NK-cell antigens such as NK-cell receptors and T-cell receptor β-chain variable region families together with TCR gene rearrangement studies. Treatment of symptomatic cytopenias in patients with indolent LGL leukemia is still based on immunosuppressive therapy. Treatment with purine analogs and alemtuzumab may be considered as an alternative option.

Progress in understanding the pathogenetic mechanisms of these entities, especially resistance of clonal LGLs to apoptosis, due to constitutive activation of survival signaling pathways, has its impact on identification of potential molecular therapeutic targets.