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

Summary 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% o...

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Bibliographic Details
Published in:British journal of haematology 2021-08, Vol.194 (4), p.701-707
Main Authors: Hines, Melissa R., Keenan, Camille, Maron Alfaro, Gabriela, Cheng, Cheng, Zhou, Yinmei, Sharma, Akshay, Hurley, Caitlin, Nichols, Kim E., Gottschalk, Stephen, Triplett, Brandon M., Talleur, Aimee C.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Antigens, CD19 - immunology
CD19 antigen
Cell therapy
Child
Child, Preschool
chimeric antigen receptor T‐cell therapy
Chimeric antigen receptors
cytokine release syndrome
Female
haemophagocytic lymphohistiocytosis
Hematology
Histiocytosis
Humans
Immune response
Immunologic Factors - therapeutic use
Immunomodulation
Immunotherapy, Adoptive - adverse effects
Lymphocytosis
Lymphohistiocytosis, Hemophagocytic - diagnosis
Lymphohistiocytosis, Hemophagocytic - etiology
Lymphohistiocytosis, Hemophagocytic - immunology
Lymphohistiocytosis, Hemophagocytic - therapy
Male
Patients
refractory acute B‐cell lymphoblastic leukaemia
Survival Analysis
Toxicity
Young Adult
Young adults
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Summary:Summary 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).
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.17662