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Severe hyperammonemia in chimeric antigen receptor T cells recipient—unusual differential diagnosis of encephalopathy syndrome

Bone Marrow Transplantation volume 57, pages 286–288 (2022)Cite this article

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Chimeric antigen receptor (CAR) T-cell therapy represents a rapidly emerging modality in cancer therapy with remarkable success in patients with relapsed/refractory B-cell lymphoid malignancies. However, the treatment is associated with neurologic complications that can be severe or even fatal, a condition called immune effector cell-associated neurotoxicity syndrome or ICANS. Clinical manifestations of ICANS range from diminished attention to mental obtundation, seizure, and life-threatening cerebral edema. The pathophysiology of ICANS remains to be elucidated and the condition is often a diagnosis of exclusion as there are no clinically validated biomarkers [1, 2].

In this report, we present an unusual case of a patient with relapsed B-cell acute lymphoblastic leukemia (ALL) who developed severe encephalopathy and refractory status epilepticus after allogeneic CD19 CAR-T cell therapy. The presentation and course were remarkably reminiscent of ICANS, however, the etiology was instead related to refractory hyperammonemia in the setting of normal liver function and the absence of an underlying genetic condition predisposing to hyperammonemia.

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Fig. 1: Timeline of treatment with allogeneic CD19 CAR-T cell and complications including ICANS, CRS, and severe hyperammonemia with refractory status epilepticus.

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Authors and Affiliations

  1. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Nuttavut Sumransub

  2. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Fiona He, Daniel Weisdorf & Veronika Bachanova

  3. Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Charles J. Billington Jr & Anjali Aggarwal

  4. Department of Neurology, University of Minnesota, Minneapolis, MN, USA

    Benjamin Miller

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  1. Nuttavut Sumransub
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  2. Fiona He
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  5. Anjali Aggarwal
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  7. Veronika Bachanova
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Contributions

NS created an outline, wrote the paper, designed and illustrated figure and table in the paper. FH, DW, CJB, AA, BM, and VB provided subspecialty consultation and critical feedback on the clinical perspective of the case and revised the paper. FH and VB devised the project and its outline, and supervised the project overall. All authors involved in patient care, read, and approved the final paper.

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Correspondence to Veronika Bachanova.

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Sumransub, N., He, F., Weisdorf, D. et al. Severe hyperammonemia in chimeric antigen receptor T cells recipient—unusual differential diagnosis of encephalopathy syndrome. Bone Marrow Transplant 57, 286–288 (2022). https://doi.org/10.1038/s41409-021-01505-5

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