Large Granular Lymphocytic Leukemia: Common Therapies and their Outcomes

Large Granular Lymphocytic Leukemia (LGLL), a rare lymphoproliferative disorder of T cell or Natural Killer cell (NK) origin is characterized by persistent immunodominant clones of CD3+ Cytotoxic T Lymphocyte (CTLs) or CD3NK cells. Dysregulated homeostasis of CTL and NK cells may be due to various pathogenic factors, including the recently identified somatic STAT3 mutations. Occurrence of severe cytopenias necessitates therapy initiation. Due to the rarity of LGL, most of the clinical experience is empiric and based on retrospective analyses. We studied the efficacy of the most frequently used agents in a clinically and molecularly annotated cohort of 152 LGLL patients. Our results demonstrate comparable primary and overall responses to oral cyclosporine A (CsA), Cyclophosphamide (CPM) and Methotrexate (MTX) regimens although the indications spectrum varied due to specific toxicities. Presence of STAT3 mutations did not affect responses or overall survival.