LAUSR

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T-lymphocytes with a terminal effectory memory phenotype (CD3 1 /CD8 1 /CD5dim/CD57 1 /CD62L/CD45RA / CD45RO 2 ) that can result in severe cytopenias, including neutropenia, anemia, and pancytopenia/bone marrow failure in severe cases. 1-3 The pathogenesis of T-LGLL is thought to be mediated by increased circulating interleukin-15, and subsequent upregulation of the STAT3 pathway, leading to dysregulation of apoptosis and resultant cellular proliferation and marrow damage. The management of T-LGLL there-fore is immune-suppressive therapy, with methotrexate (MTX), cyclophosphamide (Cy), and cyclosporine serving as the standard frontline agents. MTX is the standard frontline therapy based off the prospective ECOG5998 (E5998) study but overall response rate (ORR) was modest at 38%. 4 An initial early report with frontline Cy demonstrated a response rate of 63% in 10/16 patients, including 6 complete response (CR), though at that time, CR was de fi ned as hematologic CR, and response criteria differed from current E5998 criteria. 5 For patients that fail frontline MTX, oral Cy, with a target dose of 100 mg/day is the standard