Different Large Granular Lymphocyte Count Drew Distinguish Characteristics in Large Granular Lymphocytic Leukemia

Introduction Large granular lymphocytic leukemia (LGLL) is a rare disorder characterized by the clonal expansion of large granular lymphocytes (LGLs). While, an LGL count greater than 2×10^9/L is common, some researchers consider > 0.5×10^9/L necessary. However, the WHO and other studies do not specify a clear LGL count, leading to ambiguity. Diagnosing patients with low LGL counts, especially < 0.5×10^9/L, remains challenging. Establishing a precise clinical diagnostic parameter for LGLL is urgently needed. Methods From July 2005 to July 2022, 175 patients were diagnosed with LGLL at Blood Hospital of CAMS & PUMC.，excluding patients with aplastic anemia (AA) or other hematologic malignancies. Then patients categorized into low (<0.5× 10^9/L), intermediate (0.5-2× 10^9/L), and high (>2× 10^9/L) LGL count groups (27.4%, 31.4%, and 41.1% of patients, respectively). Results Among the 175 enrolled LGLL patients, 20 (11.4%) had NK-LGLL and 155 (88.6%) had T-LGLL. The median proportion of LGL cells was 55.8% (range: 4.1%-98.2%), with a median LGL count of 1.1 × 10^9/L (range: 0.10-71.21 × 10^9/L). The low LGL count group had 48 patients (27.4%), the intermediate group had 55 patients (31.4%), and the high group had 72 patients (41.1%). Anemia (75.0% vs. 83.6% vs. 48.6%, P<0.001), thrombocytopenia (27.1% vs. 20.6% vs. 5.6%, P<0.001), and pure red cell aplastic anemia (29.2% vs. 43.6% vs. 13.9%, P=0.001) were significantly more prevalent in the low and intermediate LGL count groups than in the high LGL count group (Table 1). Notably, Treg cell proportion was higher in the low and intermediate LGL count group compared to the high LGL count group (P=0.015). Overall, the low and intermediate LGL count groups exhibited lower overall response rates (ORR) and worse overall survival (OS) compared with the high LGL count group (ORR: 86.8% vs. 64.3% vs. 91.4%, P=0.005; OS: 3-year OS rate 86.5% vs. 90.9% vs. 100%, P=0.029). However, no evidence of a difference in ORR and OS among the three LGL count groups was observed under treatment subgroups. Conclusions Generally, while LGL counts reveal unique clinical and biological features, they should not be obligatory for diagnosing LGLL.