{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:45:48Z","timestamp":1793148348312,"version":"4.5.0"},"reference-count":31,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 \u00b5g\/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 &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers18101594","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:04:09Z","timestamp":1778763849000},"page":"1594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis Following CAR T-Cell Therapy: Results of a Real-World Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Inna","family":"Shaforostova","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Noelle","family":"Kronig","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-1573","authenticated-orcid":false,"given":"Katja","family":"Seipel","sequence":"additional","affiliation":[{"name":"Department for Biomedical Research, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-4753","authenticated-orcid":false,"given":"Alicia","family":"Rovo","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-947X","authenticated-orcid":false,"given":"Ulrike","family":"Bacher","sequence":"additional","affiliation":[{"name":"Department of Hematology and Central Hematology Laboratory, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-5257","authenticated-orcid":false,"given":"Thomas","family":"Pabst","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Inselspital Bern University Hospital, University of Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1182\/blood.2024025378","article-title":"Boosting CAR T cells against lymphomas","volume":"144","author":"Pabst","year":"2024","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sanoyan, D.A., Seipel, K., Bacher, U., Kronig, M.-N., Porret, N., Wiedemann, G., Daskalakis, M., and Pabst, T. 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