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01.12.2016 | Letter to the Editor | Ausgabe 1/2016 Open Access

Journal of Hematology & Oncology 1/2016

Predominant cerebral cytokine release syndrome in CD19-directed chimeric antigen receptor-modified T cell therapy

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2016
Autoren:
Yongxian Hu, Jie Sun, Zhao Wu, Jian Yu, Qu Cui, Chengfei Pu, Bin Liang, Yi Luo, Jimin Shi, Aiyun Jin, Lei Xiao, He Huang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13045-016-0299-5) contains supplementary material, which is available to authorized users.

Abstract

Chimeric antigen receptor-modified (CAR) T cells targeting CD19 (CART19) have shown therapeutical activities in CD19+ malignancies. However, the etiological nature of neurologic complications remains a conundrum. In our study, the evidence of blood-brain barrier (BBB)-penetrating CAR T cells as a culprit was revealed. A patient with acute lymphocytic leukemia developed sustained pyrexia with tremors about 6 h after CART19 infusion, followed by a grade 2 cytokine release syndrome (CRS) and neurological symptoms in the next 3 days. Contrast-enhanced magnetic resonance showed signs of intracranial edema. Lumbar puncture on day 5 showed an over 400-mmH2O cerebrospinal pressure. The cerebrospinal fluid (CSF) contained 20 WBCs/μL with predominant CD3+ T cells. qPCR analysis for CAR constructs showed 3,032,265 copies/μg DNA in CSF and 988,747 copies/μg DNA in blood. Cytokine levels including IFN-γ and IL-6 in CSF were extremely higher than those in the serum. Methyprednisone was administrated and the symptoms relieved gradually. The predominance of CART19 in CSF and the huge discrepancies in cytokine distributions indicated the development of a cerebral CRS, presumably featured as CSF cytokines largely in situ produced by BBB-penetrating CAR T cells. For the first time, we reported the development of cerebral CRS triggered by BBB-penetrating CAR T cells.
Trial registration: ChiCTR-OCC-15007008.

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Zusatzmaterial
Additional file 1: Detailed patient information and procedures of diagnosis and treatment. (DOCX 17.2 KB)
13045_2016_299_MOESM1_ESM.docx
Additional file 2: Preparation of chimeric antigen receptor-modified (CAR) T cells targeting CD19 (CART19). (DOCX 16.7 KB)
13045_2016_299_MOESM2_ESM.docx
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