Large granular lymphocytic leukemia. Current diagnostic and therapeutic approaches and novel treatment options

Large granular lymphocytic leukemia (LGLL) is a low grade lymphoproliferative disorder characterized by the clonal proliferation of large granular lymphocytes (LGL) and recognised by the WHO. The diagnosis and management of these patients is challenging due to the limited information from prospective studies. Guidelines for front-line therapy have not been established. The prognosis is favourable with median overall survivals greater than 10 years. Areas covered: This manuscript is a review of the clinical features, diagnosis, pathogenesis and, in particular, the various available therapeutic options for this rare lymphoid leukemia. A systematic literature search using electronic PubMed database has been carried out. Expert commentary: A watch and wait strategy without therapeutic intervention is recommended in asymptomatic patients. The immunomodulators methotrexate, cyclophosphamide and cyclosporin are the most commonly used drugs in the routine practice with responses ranging from 50 to 65% and without evidence of cross-resistance among them. Purine analogs such as 2´deoxycoformycin and fludarabine alone or in combination may be indicated in patients with bulky and/or widespread disease. Trials using monoclonal antibodies such as Alemtuzumab and agents targeting the disrupted JAK/STAT pathway in LGLL such as JAK-3 inhibitors are promising particularly in a relapse setting.