Involvement of bone marrow, liver, spleen and extranodal number were associated with poor outcome in angioimmunoblastic T-cell lymphoma (AITL) patients

Abstract Background ： Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct subtype of peripheral T-cell lymphoma (PTCL). Primarily affecting elderly patients, AITL presents with progressive lymphadenopathy, hepatosplenomegaly, systemic symptoms including fever and fatigue, along with cutaneous manifestations, anemia, and hypergammaglobulinemia. The disease course demonstrates aggressive progression and significant heterogeneity. Approximately one-quarter of patients exhibit multi-site involvement, with the spleen, liver, lungs, and skin being the most frequently affected areas. Notably, skin eruptions (13.1%) and pleural/peritoneal effusions (14.1%) appear to be unique autoimmune features specific to AITL. However, whether the extent and number of extranodal lesions correlate with prognosis remains unclear. purpose ： Explore the relationship between extracollegiate involvement sites/ number and PFS/OS to better guide clinical prognosis judgment and diagnosis and treatment. Method ： A total of 350 patients with AITL enrolled in the study were conducted from 4 medical centers, from August 2015 to November 2023. Methods including univariate analysis, LASSO regression, multivariate Cox regression, and K-M curve were used to analyze the effects of extranodal involvement sites and numbers on PFS and OS in AITL patients. Results： We analyzed the locations and numbers of extranodal involvement in multicenter 350 AITL patients. Multivariate analysis revealed significant correlations between liver, spleen, and bone marrow involvement with PFS (HR (95% CI): liver 1.72 [1.06-2.79], P<0.0278; spleen 1.49 [1.11-2.00], P<0.0075; bone marrow 1.83 [1.41-2.38], P<0.0001) and OS (liver 1.59 [1.00-2.52], P<0.0488; spleen 2.07 [1.47-2.92], P<0.0001; bone marrow 2.25 [1.69-2.99], P<0.0001). The total number of extranodal sites was also associated with PFS and OS. Notably, an Extranodal involvement count ≥2 was closely linked to prognosis (PFS: 2.22 [1.59-3.11], P<0.0001). LASSO regression modeling using lesion distribution as a risk factor identified liver, spleen, and bone marrow involvement as key prognostic factors in both PFS and OS models. Through multivariate Cox regression analysis, after adjusting for gender, age, ECOG score, β2-MG, and LDH levels, it showed that liver involvement, bone marrow involvement, and extranodal sites ≥2 were identified as independent prognostic factors for PFS. Conversely, spleen involvement, bone marrow involvement, and extranodal sites ≥2 were associated with OS. Furthermore, the Kaplan-Meier survival curves demonstrated that patients with liver, spleen, or bone marrow involvement, along with extranodal sites ≥2, exhibited significantly poorer PFS and OS outcomes. Conclusion ： Liver, spleen and bone marrow involvement are prognostic factors for PFS and OS in AITL patients. The more extranodal sites there are, the worse the prognosis, and the more than 2 extranodal sites is an independent prognostic factor for PFS and OS. Keyword ： Angioimmunoblastic T-cell lymphoma (AITL), liver, spleen, bone marrow, prognosis