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Large granular lymphocytic leukaemia pathogenesis and management

The WHO classification recognises three distinct disorders of large granular lymphocytes: T‐cell large granular lymphocytic leukaemia (T‐LGL), chronic lymphoproliferative disorders of NK‐cells (CLPD‐NK) and agressive NK‐cell leukaemia. Despite the different cell of origin, there is considerable overlap between T‐LGL and CLPD‐NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK‐cell leukaemia and the rare CD56+ aggressive T‐LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease.