CELL INTELLIGENCE · 肿瘤细胞治疗研究

Background : Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) is a rare, life-threatening complication following CAR T-cell therapy. Diagnosis is challenging due to overlap with severe CRS, sepsis and lack of standardized criteria. Clinical data remain limited. Methods : We retrospectively analyzed 301 patients treated with CD19- or BCMA-directed CAR T-cells for hematologic malignancies at a single center from January 2019 to January 2026. IEC-HS was defined according to American Society for Transplantation and Cellular Therapy criteria. Results : Median follow-up was 31 months. IEC-HS was diagnosed in 14 patients (4. 7%), median age 67 years. Underlying diseases included diffuse large B-cell lymphoma ( n = 4), multiple myeloma ( n = 7), mantle cell lymphoma, Burkitt lymphoma and B-lymphoblastic leukemia ( n = 1 each). All patients had hyperferritinemia and cytopenias at baseline; most had high tumor burden (9/14) and elevated LDH (10/14).

CRS occurred in all patients and ICANS in 6/14. IEC-HS occurred at median 10 days and was characterized by hyperferritinemia (median 15,321 g/L), neutropenia, thrombocytopenia, hepatic dysfunction and high CAR-T-cell expansion in peripheral blood. Treatment included corticosteroids and anakinra (12/14). Refractory patients received IVIG (5/14), tocilizumab (3/14), siltuximab, ruxolitinib, emapalumab or etoposide (each n = 1). Infections occurred in 11/14; 4/14 had mixed infections.

IEC-HS resolved in 7/14 (median 7 days). Mortality was 79% (11/14), mainly due to IEC-HS (7/14). Three patients were alive at last follow-up. One-year OS was lower vs. the whole cohort (31% vs. 69%, p < 0. 0001). Conclusions : IEC-HS was associated with severe cytopenias, hyperferritinemia, hepatic dysfunction and high infection risk. Despite intensive immunosuppressive therapy, outcomes remain poor. Early biomarker-driven identification and multicenter studies are needed.