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Hemophagocytic lymphohistiocytosis‐like toxicity (carHLH) after CD19‐specific CAR T‐cell therapy

Melissa Hines, Camille Keenan, Gabriela Marón, Cheng Cheng, Yinmei Zhou, Akshay Sharma, Caitlin Hurley, Kim E. Nichols, Stephen Gottschalk, Brandon M. Triplett, Aimee C. Talleur

2021British Journal of Haematology121 citationsDOIOpen Access PDF

Abstract

Chimeric antigen receptor T-cell (CAR T-cell) therapy is associated with significant toxicities secondary to immune activation, including a rare but increasingly recognised severe toxicity resembling haemophagocytic lymphohistiocytosis (carHLH). We report the development of carHLH in 14·8% of paediatric patients and young adults treated with CD19-specific CAR T-cell therapy with carHLH, occurring most commonly in those with high disease burden. The diagnosis and treatment of carHLH required a high index of suspicion and included multidrug immunomodulation with variable response to therapies. Compared to patients without carHLH, patients with carHLH had both reduced response to CAR T-cell therapy (P-value = 0·018) and overall survival (P-value = < 0·0001).

Topics & Concepts

Chimeric antigen receptorMedicineToxicityCell therapyHemophagocytic lymphohistiocytosisT cellImmunologyInternal medicineImmune systemDiseaseCellBiologyGeneticsCAR-T cell therapy researchImmune Cell Function and InteractionAutoimmune and Inflammatory Disorders Research