Abstract
Background: T-LGL is a rare and indolent lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T cells. Although typically considered a chronic disease, T-LGL demonstrates substantial clinical and biological heterogeneity, with presentations ranging from asymptomatic cases to severe cytopenias, recurrent infections, and autoimmune phenomena, particularly rheumatoid arthritis. Due to its low incidence and variable presentation, most current knowledge is derived from small retrospective series, limiting the ability to clearly define prognostic factors and optimal therapeutic strategies. Comprehensive analyses of real-world data are therefore needed to better elucidate the clinicopathologic determinants that impact survival and inform evidence-based management of this challenging disease. This study aims to address these gaps by evaluating survival determinants in a large pooled database of T-LGL patients.
Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled and analyzed a pooled real-world database of cases that satisfy the diagnostic criteria for T-LGL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS).
Results:
A total of 132 patients were included in the analysis. The median age was 57, with no sexual preponderance. Autoimmune disorders were present in 56%, and TCR was clonal in 95% (TCRαβ+ 70%). While 60% were alive at 15 years, the median DFS was 36months. Constitutionals symptoms, infections, and splenomegaly were detrimental to OS. Time to diagnosis correlated positively with OS. OS was not impacted by age, blood counts including LGL, %BM involvement, ↑LDH, RF/ANA/DAT+, presence of monoclonal gammopathy or hepatomegaly, and type of TCR. OS was numerically worse in Males, LN+, CD4-, CD56+, ↓albumin, but better in presence of Rheumatoid arthritis, though none research statistical significance. While there was no additive impact for combined chemotherapy on OS, including CSA and MTX in the course of treatment did improve OS. Patients who did not achieve CR had worse survival.
Conclusions:
This real-world analysis identified key clinical and therapeutic factors influencing overall survival in T-LGL. The presence of constitutional symptoms, infections, and splenomegaly was associated with a poorer prognosis, while the inclusion of immunosuppressive agents, such as cyclosporine and methotrexate, was linked to improved outcomes. Achieving complete remission was a critical determinant of survival. These findings provide important insights into risk stratification and highlight the need for individualized, evidence-based management strategies to optimize outcomes in this rare and heterogeneous disease.
