Prolonged severe cytopenia followed by fatal CAR T-cell-mediated encephalitis in a patient with acute lymphoblastic leukemia.

Autor:	Koike T; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Toyama D; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Shibata M; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Otsuka K; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Sugishita Y; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Kaneko R; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Kawabata N; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Fujita S; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Akiyama K; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan., Yamamoto S; Department of Pediatrics, Tokai University School of Medicine, Kanagawa, Japan.
Jazyk:	angličtina
Zdroj:	Blood cell therapy [Blood Cell Ther] 2024 Oct 11; Vol. 7 (4), pp. 118-120. Date of Electronic Publication: 2024 Oct 11 (Print Publication: 2024).
DOI:	10.31547/bct-2024-010
Abstrakt:	Immune effector cell-associated neurotoxicity syndrome usually occurs within the first four weeks of chimeric antigen receptor (CAR)-T cell therapy. In addition, prolonged cytopenia is a long-term adverse effect following the use of CAR T-cell therapies. Here, we present a case of prolonged severe cytopenia followed by fatal CAR T-cell-mediated encephalitis. A 22-year-old male patient was referred to our hospital for a second relapse of B-cell precursor acute lymphoblastic leukemia (ALL), which was diagnosed 22 months after hematopoietic stem cell transplantation from an unrelated donor. CAR T-cells (tisagenlecleucel) were infused during the third cycle of complete remission after chemotherapy. The patient developed grade 2 cytokine release syndrome requiring a single dose of tocilizumab. Cytopenia was profound from day 30 onward, but no other serious complications were observed. On day 50, the patient developed sensory impairment, disturbing behavior, and confusion. Brain magnetic resonance imaging (MRI) scan and cerebrospinal fluid (CSF) analysis revealed no pathological findings. Severe neutropenia persisted despite G-CSF treatment, and the patient's neurological symptoms rapidly progressed from day 65. Brain MRI revealed hydrocephalus. The CSF showed elevated xanthochromia, mononuclear cell counts, and protein levels. A therapeutic attempt with prednisolone for encephalitis was ineffective, and the patient died on day 77 owing to neurological toxicity. Late-onset CAR T-cell-mediated encephalitis was suspected, although the CSF was not assessed for CAR T-cells. In addition, the patient developed prolonged and severe cytopenia. To the best of our knowledge, this is the first report of prolonged severe cytopenia followed by late-onset CAR T-cell-mediated encephalitis. These unexpected long-term adverse effects may occur and should also be considered. Competing Interests: The authors declare no conflict of interest. Disclosure forms provided by the authors are available on the website. (Copyright Ⓒ2024 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)
Databáze:	MEDLINE
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