Clinical features and prognostic impact of hemophagocytic lymphohistiocytosis in angioimmunoblastic T-cell lymphoma: a single-center retrospective study

Abstract Background: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive nodal T-follicular helper-cell lymphoma with prominent immune dysregulation. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. However, the clinical characteristics and prognostic impact of AITL-associated HLH (AITL-HLH) remain unclear. Methods: We retrospectively analyzed 70 consecutive patients with AITL diagnosed between January 2015 and January 2025. Clinical features, laboratory findings, treatment regimens, and outcomes were compared according to HLH status. Results: Of the 70 patients, 23 (32.9%) developed AITL-HLH,5 (21.7%) before AITL diagnosis, 9 (39.1%) synchronously, and 9 (39.1%) more than 30 days after AITL diagnosis. Compared with patients without HLH, those with HLH more frequently had fever, B symptoms, Ann Arbor stage IV disease, bone-marrow hemophagocytosis, anemia, thrombocytopenia, hypoalbuminemia, hyperferritinemia, and peripheral-blood EBV-DNA positivity (P < 0.05). Median overall survival (19.2 vs 46.1 months; P = 0.037) and progression-free survival (9.6 vs 31.6 months; P = 0.038) were shorter in the HLH group, whereas lymphoma response rates were similar. Multivariable analysis identified poorer Eastern Cooperative Oncology Group performance status (HR 2.31; P = 0.038), higher direct bilirubin (HR 1.03 per 1 μmol/L; P < 0.001), and lower platelet count (HR 0.95 per 10 × 10⁹/L; P = 0.021) as independent adverse factors. Conclusions: AITL-HLH is an aggressive and temporally heterogeneous inflammatory phenotype. Peripheral-blood EBV-DNA positivity, rather than quantitative viral burden, was associated with HLH. A favorable short-term response of HLH does not necessarily translate into prolonged survival. Early recognition and prompt control of hyperinflammation and lymphoma are essential.