Γδ and Αβ T-Cell Large Granular Lymphocytic Leukemia Have Similar Characteristics and Outcomes
Authors: Yuxi Li , Cui Rui , Yu Ying , Huang Yanshan , Sun Jingwen , Yan Yuting , Wang Tingyu , Wenjie Xiong , Lyu Rui , Wang Qi , LIU Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Zou Dehui , Zhang Fengkui , Wang Huijun , Xiao Zhi-jian , Qiu Lu-Gui , Yi Shuhua 
Published: December 2024

Introduction
Large granular lymphocytic leukemia (LGLL) is a rare chronic lymphoproliferative disorder characterized by persistent clonal expansions of lymphocytes over an extended period in which nearly 80% of cases are T-cell large granular lymphocytic leukemia (T-LGLL) (Alaggio et al. 2022). The clinical and biological features of T-LGLL exhibit significant heterogeneity as it can manifest as either CD8+ or CD4+. Furthermore, T-LGLL is associated with the rearrangement of the T cell receptor (TCR), which can be categorized into αβ T-LGLL and γδ T-LGLL variants. Additionally, few studies have compared αβ T-LGLL and γδ T-LGLL displaying that γδ T-LGLL revealed a similar or more aggressive clinical manifestation than αβ T-LGLL (Bourgault-Rouxel et al. 2008; Sandberg et al. 2006; Barilà et al. 2020; Barila et al. 2023). Thus, in this study, we described the clinical and biological features of 56 γδ T-LGLL patients, comparing to 306 αβ T-LGLL patients from a single institute.
Methods
A total of 362 patients with a diagnosis of T-LGLL between July 2005 and July 2022 from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science. All the patients met the recommended diagnostic criteria for LGLL(Lamy, Moignet, and Loughran 2017). We conducted a retrospective analysis of patients' clinical data, laboratory examinations, treatment, and follow-up. Non-normal distribution data were expressed as a median and range. Comparisons of continuous variables in different subgroups were analyzed with the Mann-Whitney U test. A χ2 or Fisher exact test was used to compare categorical variables. OS and PFS was calculated using the Kaplan-Meier method and compared by the log-rank test. P value &lt; 0.05 was considered significant. Follow-up was to death or all statistical analyses were performed using the statistical software SPSS 27.
Results
Out of the 362 consecutive patients identified with T-LGLL, 56 (7.5%) were γδ T-LGLL, while 306 (92.5%) were αβ T-LGLL. Overall, clinical findings were very similar between the two groups in terms of median age (55 vs 54, P = 0.536), sex ratio (1.2 vs 1.3, P = 0.543), severity of neutropenia [absolute neutrophil count (ANC) ≤ 1.5×109 /L: 53.5% vs 53.3%, P = 0.959], anemia [hemoglobin (HB) ≤ 120 g/L: 85.7% vs 79.4%, P = 0.275], thrombocytopenia [Platelet (PLT) ≤ 100×109 /L: 14.3% vs 15.4%, P = 0.837], splenomegaly (32.7% vs 37.6%, P = 0.497), and pure red blood cell aplastic anemia (32.1% vs 39.9%, P = 0.275). Additionally, no significant differences were found between γδ and αβ T-LGLL cases in the frequency of STAT3 mutation (54.2% vs. 39.1%, P = 0.168). However, CD4-/CD8- immunophenotype was more frequent in the γδ T-LGLL cohort compared to αβ T-LGLL (25% vs. 17.6%; P &lt; 0.001).
Among the 362 patients, 309 patients (85.3%) required treatment. About 50% of patients received cyclosporine (CsA) and nearly 30% of patients had methotrexate (MTX) in both groups. Our analysis revealed that the overall response rate (ORR) of CsA was higher in the γδ T-LGLL subtype compared to the αβ T-LGLL (ORR: 78.6% vs. 58.7%, P = 0.048), when no significant difference in ORR of MTX was found (ORR: 78.5% vs. 85.2%, P = 0.684). After a median follow-up of 48.8 months for γδ T-LGLL and 53.1 months for αβ T-LGLL, the median overall survival (OS) was not reached in either subtype. There was no difference in median OS between γδ T-LGLL and αβ T-LGLL (152.5 vs. 158.4 months, P = 0.525). Hb ≤ 90g/L, PLT ≤ 150×10^9/L, and the co-existence of other malignancies were associated with decreased OS by univariate analysis in 362 T-LGLL patients.
Conclusion
In conclusion, patients with γδ T-LGLL exhibited comparable clinical and biological characteristics to those with αβ T-LGLL subtypes. Both subtypes had similar response to CsA or MTX-based therapy. No statistically significant differences in OS were observed between the two subtypes. It is advisable to employ identical therapeutic strategies for the treatment of both γδ T-LGLL and αβ T-LGLL in future clinical practice.