Haema 2010; 1(1): 52-59
by M. Spanoudakis, C. Kalpadakis and H. Papadaki
Department of Haematology, University of Crete, School of Medicine
Abstract
Clonal disorders of large granular lymphocytes (LGL) comprise a relatively rare spectrum of lymphoproliferative diseases originating from mature T- or natular killer (NK) cells. According to their clinical presentation, four clinical subtypes have been recognized: indolent LGL leukemias of T-cell or NK-cell origin and the aggressive respective ones. The most common form is the indolent Tcell LGL leukemia which is usually characterized by the presence of one or more cytopenias. The etiology remains unclear. Chronic antigenic stimulation (autoantigens or viral) leading to activation of T cells have been implicated in disease pathogenesis. Diagnosis is mainly based on the identification of clonality along with expression of characteristic immunophenotype and on specific clinical findings, if present. Immunosuppressive therapy with low dose methotrexate, cyclophosphamide or cyclosporine A with or without steroids is effective for the management of cytopenias. Haemopoetic growth factors are also used in this setting. The refractory forms can be managed with alemtuzumab, purine analogues or splenectomy in selected cases. The aggressive variant is usually refractory to conventional chemotherapy and more intensive, acute lymphoblastic leukaemia-like regimens have been used as well as allogenic stem cell transplantation.