T gamma delta LGLL identifies a subset with more symptomatic disease: analysis of an international cohort of 137 patients

T gamma delta large granular lymphocyte leukemia (LGLL) is a rare variant of T-cell LGLL (T-LGLL) that has been less investigated as compared with the more frequent T alpha beta LGLL, particularly in terms of frequency of STAT3 and STAT5b mutations. In this study, we characterized the clinical and biological features of 137 patients affected by T gamma delta LGLL; data were retrospectively collected from 1997 to 2020 at 8 referral centers. Neutropenia and anemia were the most relevant clinical features, being present in 54.2% and 49.6% of cases, respectively, including severe neutropenia and anemia in similar to 20% of cases each. Among the various treatments, cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 cases were available for STAT3 and STAT5b mutation analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of T gamma delta cases were also compared with a recently published T alpha beta cohort including 129 cases. Though no differences in STAT3 and STAT5b mutational frequency were found, T gamma delta cases more frequently presented with neutropenia (P = .0161), anemia (P < .0001), severe anemia (P = .0065), and thrombocytopenia (P = .0187). Moreover, V delta 2-cases displayed higher frequency of symptomatic disease. Overall, T gamma delta cases displayed reduced survival with respect to T alpha beta cases (P = .0017). Although there was no difference in STAT3 mutation frequency, our results showed that T gamma delta LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared with T alpha beta LGLL.