Distinct CD8⁺/CD57⁺ Large Granular Lymphocytic Populations Seen by Flow Cytometry Are Associated with Monoclonal T-Cell Populations, a Retrospective Case-Control Study of Large Granular Lymphocytic Leukemia

Abstract 2707

Large granular lymphocytic (LGL) leukemia is a disease with chronic elevations of large granular lymphocytes for > 6 months associated with a T-cell clone and often cytopenias. While a defined classification has been established in the 2008 WHO, the clinical and pathologic diagnosis often remains elusive, as patients can exhibit significant polyclonal or oligoclonal proliferations of LGLs in reactive conditions. Therefore predicting and defining patients with increased LGLs and significant monoclonal proliferations remains difficult. In an attempt to identify flow cytometry patterns which might be associated with monoclonality, we performed a retrospective review of patients at our institute between 2003–2010 with significant populations of peripheral blood LGLs in which T-cell clonality tests were also performed. 66 independent cases were identified and were divided impartially by time into a study set (cases from 2008–2010) and an experimental set (cases from 2003–2007). In the study set (2008-2010), 31 flow cytometry cases were identified, which stratified into 16 cases with monoclonal T-cell populations and 15 with oligoclonal or polyclonal populations. Comparing flow cytometry scatter-plots, we identified what appeared to be a discrete flow cytometry pattern. Specifically, those cases with distinct CD8+(dim)/CD57+ populations were significantly associated with T-cell monoclonality (p =< 0.0001) as well as lower neutrophil counts (average ANC= 1.78, p < 0.001) (See Figure 1). Such a preliminary analysis suggested that identification of patients with specific CD8+(dim)/CD57+ populations might define patients with not only monoclonal proliferations, but also with clinically and pathologically significant disease. To further evaluate this hypothesis, we used these criteria (discrete CD8+(dim)/CD57+ populations) to examine, in a blinded analysis, our experimental set of 35 consecutive cases of large granular lymphocytosis from 2003–2007. 11 cases were identified which demonstrated significant CD8+(dim)/CD57+ populations. Yet again, we observed that distinct populations of CD8+(dim)/CD57+ populations were associated with T-cell monoclonality (p =0.037), as well as neutropenia (average ANC=1.49; p=0.046). These findings demonstrate and define a major subset of clinically and pathologically significant patients through the use of flow cytometry immunophenotyping.

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