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Review
. 2025 Aug;32(2):213.
doi: 10.3892/mmr.2025.13578. Epub 2025 May 26.

Chimeric antigen receptor T cell immunotherapy‑associated hemophagocytic lymphohistiocytosis: Pathogenesis, clinical manifestation, diagnosis and management compared with cytokine release syndrome (Review)

Jinglin Hu  1 , Cuicui Feng  1 , Lingbo He  2 , Yini Wang  1
Affiliations
Review

Chimeric antigen receptor T cell immunotherapy‑associated hemophagocytic lymphohistiocytosis: Pathogenesis, clinical manifestation, diagnosis and management compared with cytokine release syndrome (Review)

Jinglin Hu et al. Mol Med Rep. 2025 Aug.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is used to treat hematological malignancy. However, it carries the risk of life‑threatening inflammatory toxicity, including cytokine release syndrome (CRS) and CAR T cell‑associated hemophagocytic lymphohistiocytosis (CARHLH). CRS is a common side effect of CAR T cell therapy, with fever and multiorgan functional impairment as the primary clinical manifestation. CARHLH and CRS have similar clinical manifestations. However, CARHLH is associated with a high mortality rate. CARHLH was previously considered a specific type of CRS, however, it must be promptly differentiated from CRS for treatment initiation, with management differing from that of CRS. The pathogenesis of CARHLH differs from that of CRS. The present review aimed to summarize the pathogenesis, diagnosis and treatment of CARHLH to assist in its early identification and management.

Keywords: chimeric antigen receptor T cell immunotherapy; chimeric antigen receptor T cell‑associated hemophagocytic lymphohistiocytosis; cytokine release syndrome; diagnosis; hemophagocytic lymphohistiocytosis; treatment.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
Pathogenesis of cytokine release syndrome.
Figure 2.
Figure 2.
Potential pathogenesis of CARHLH. CARHLH, chimeric antigen receptor T cell-associated hemophagocytic lymphohistiocytosis; NK, natural killer.
See this image and copyright information in PMC

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