Classification of NK-Large Granular Lymphocytic Leukemia By CD56 Expression

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.4439-4439
• Main Authors: Li, Yuxi, Yuan, Jingjing, Cui, Rui, Yu, Ying, Huang, Yanshan, Yan, Yuting, Sun, Jingwen, Wang, Tingyu, Lyu, Rui, Wenjie, Xiong, Wang, Qi, LIU, Wei, An, Gang, Sui, Weiwei, Xu, Yan, Huang, Wenyang, Zou, Dehui, Zhang, Fengkui, Wang, Huijun, Qiu, Lugui, Yi, Shuhua
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-201476

Introduction Large granular lymphocytic leukemia (LGLL) is a rare chronic lymphoproliferative disease of T cell and natural killer (NK) cell lineage. Less than 10% of cases are NK-large granular lymphocytic leukemia (NK-LGLL) (Zawit et al. 2021). Mature NK cells could be divided into two subsets, CD56dim and CD56bright. The CD56dim NK-cell subset exhibits a higher level of natural cytotoxic activity compared to the CD56bright NK-cell subset, which, in turn, is capable of producing abundant cytokines (Cooper, Fehniger, and Caligiuri 2001). In this study, we conducted an analysis of a large cohort with 47 NK-LGLL patients, finding that patients presenting CD56 dim or negative expression on NK-LGLs had more severe symptoms and worse outcomes. Methods Between January 2014 and July 2023, 47 patients diagnosed with NK-LGLL were collected from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. All the patients met the recommended diagnostic criteria for LGLL(Lamy, Moignet, and Loughran 2017). NK subtype was defined by flow cytometry analysis using common surface markers showing CD3−/CD16+, or CD56+ pattern, and cells were considered antigen partial positive if CD56 antibody staining was between 20%-80%. To perform subgroup analysis, we incorporated partial CD56 positive into the negative group since mature NK cells are CD56-positive. Results With regards to clinical and biological features of the 47 NK-LGLL cases, more than half of the patients (61.7%) presented symptoms (including cytopenia and splenomegaly) at the time of visit, among which anemia was the primary clinical manifestations observed in 57.4%. Pure red cell aplasia (PRCA) was found in 14.0%. 23 of 37 (62.2%) did not exhibit any of the five assessed KIR, when the remaining (37.8%) showed a restrictive pattern, predominantly of CD158i (27.0%). The next generation sequencing was available for 32/47 (68.1%) patients, STAT3 (13/32, 40.6%) was the most frequently mutated gene. With a median follow-up of 56.2 months (range 6.7 to 112.3 months), more than half (27/47, 57.4%) of patients required treatment. The 5-year OS was 95.2%. The median number of treatment lines was 1 (range 1-4). MTX-based therapy and CsA-based therapy were delivered in 51.9% (14/27) patients and 29.6% of patients, respectively, as a first-line treatment, when no significant difference in response rate were found between the two therapies (ORR: 85.7% vs 87.5%,