Tγδ LGL LEUKEMIA IDENTIFIES A SUBSET WITH MORE SYMPTOMATIC DISEASE: ANALYSIS OF AN INTERNATIONAL COHORT OF 137 PATIENTS.

Tgd LGL Leukemia (Tgd LGLL) is a rare variant of T-LGLL that has been less investigated as compared with the more frequent Tab 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 Tgd LGLL retrospectively collected at 8 referral centers and collected from 1997 to 2020. 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 around 20% of cases each. Among the various treatments, Cyclosporine A was shown to provide the best response rates. DNA samples of 97 and 94 patients were available for STAT3 and STAT5b mutations analysis, with 38.1% and 4.2% of cases being mutated, respectively. Clinical and biological features of our series of Tgd patients were also compared with a recently published Tab cohort including 129 patients. Though no differences in STAT3 and STAT5b mutational frequency were found, Tgd cases more frequently presented with neutropenia (p=0.0161), anemia (p<0.0001), severe anemia (p=0.0065) and thrombocytopenia (p=0.0187). Moreover, Vd2 negative patients displayed higher frequency of symptomatic disease. Overall, Tgd patients displayed reduced survival with respect to Tab patients (p=0.0017). Although there was no difference in STAT3 mutation frequency, our results showed that Tgd LGLL represents a subset of T-LGLL characterized by more frequent symptoms and reduced survival as compared to Tab LGLL.