Background
T-cell large granular lymphocyte leukemia (T-LGL) is a chronic lymphoproliferative disorder characterized by clonal expansion of cytotoxic T-cells and cytopenia of one or more myeloid lineages1. Despite a typically indolent nature, most patients eventually require treatment because of severe cytopenias, caused by either direct (cellular-mediated) or indirect (cytokines) attack of myeloid precursors by the clonal T-cells.1,2Because T-LGL in its severe form is a rare condition, no head-to-head comparisons of different treatment options have been conducted. Guided by single-arm studies, three drugs – methotrexate (MTX), cyclosporine (CsA), or cyclophosphamide (Cy) - are routinely used as first-line therapies. Overall response rates (ORR) have been reported at 38%-60% for MTX, 45%-92% for CsA and 47%-72% for Cy2,3, and a recent retrospective analysis reported comparable ORR of 61.5%-74.4% for all three agents.4 Even less data exist as to the management of refractory cases. Several drugs inhibiting epigenetic repressing enzymes of the histone deacetylase (HDAC) class are approved for treating other peripheral T-cell malignancies, and a case-report described the successful use of the HDAC-inhibitor belinostat (1000 mg/m2 intravenously, days 1-5 in 21-day cycles) to produce red-cell transfusion independence in a patient with T-LGL and anemia refractory to MTX, CsA and Cy.5 HDAC-inhibitors, however, cause cytopenias in their own right, via cytotoxic or cytostatic actions possibly inherent to HDAC-inhibition, which can undermine the cytopenia-correction goal-of-care. We describe here an elderly patient with T-LGL with red cell transfusion-dependence refractory to several lines of therapy including an HDAC-inhibitor, who was successfully treated with the drug decitabine administered by a regimen designed to inhibit/deplete the epigenetic repressing enzyme DNA methyltransferase 1 (DNMT1) without cytotoxicity.6-9