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