Cervical Edema Extending to the Larynx as Local Cytokine Release Syndrome Following Chimeric Antigen Receptor T-Cell Therapy in a Boy with Refractory Acute Lymphoblastic Leukemia

Abstract

Cytokine release syndrome (CRS) is one of the major acute complications caused by massive cytokine release after chimeric antigen receptor (CAR) T-cell therapy. Patients with tumor masses were considered at high risk of local CRS induced by the expansion of CAR T cells in the tumor masses. However, even patients without any tumor burden around the neck are at risk of developing cervical edema as local CRS, which can lead to life-threatening airway obstruction. Here, we present the case of a 15-year-old boy who developed cervical edema as a local CRS after CAR T-cell therapy for refractory acute lymphoblastic leukemia. Despite administration of tocilizumab and methylprednisolone for persistent fever as a symptom of systemic CRS after CAR T-cell therapy, cervical edema occurred and extended to the larynx, resulting in dysphagia and hoarseness. Dexamethasone was remarkably effective, and the laryngeal symptoms resolved within a few hours. Local cytokine syndrome showed exacerbation with tocilizumab but exhibited considerable improvement with dexamethasone administration.

Cervical Local Cytokine Release Syndrome Following Chimeric Antigen Receptor T-cell Therapy in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

“…The other possibility is that local CRS is attributed to localized acute inflammation caused by CAR-T cell redistribution to non-tumorous tissues. Indeed, there are reports of local CRS occurring in non-tumorous cervical areas, such as our cases, implying a link between local CRS and an abundance of normal lymphoid tissues in the cervical area [ 10 , 11 ]. Furthermore, local CRS was preceded by systemic CRS in our cases.…”

“…In contrast to systemic CRS, local CRS is uncommon and has only been reported sporadically in patients receiving CAR-T therapy for various malignancies, including ovarian cancer, B-cell lymphoma, and B-cell acute lymphocytic leukemia (B-ALL) [10][11][12][13]. However, the local CRS's precise mechanism has not been fully elucidated.…”

“…Compared to these prevalent systemic symptoms of CRS, an acute inflammatory phenomenon at specific body regions, named local CRS, is a rare complication. However, data on local CRS is scarce [10][11][12][13]. We here present two patients who developed local CRS with significant cervical edema following anti-CD19 CAR-T therapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).…”

Rare Adverse Events of CAR T-Cell Therapy

“…A 15-year-old boy with refractory ALL exhibited persistent high fever (>39 °C) from Day 1 after infusion of tisacel. 35 Despite tocilizumab and methylprednisolone administration, cervical edema extended to the larynx on Day 3, causing dysphagia and hoarseness, but resolved within hours after dexamethasone treatment. The fever gradually subsided from Day 8, and the patient sustained remission for 15 months after infusion.…”

CT Demonstration of Local Cytokine-Release Syndrome Involving the Head and Neck Following Chimeric Antigen Receptor T Cell Infusion Therapy

“…Cytokine release syndrome (CRS) is a clinical syndrome that results from systemic immune activation, chimeric antigen receptor T (CAR-T) cell expansion, and increased levels of serum inflammatory markers and cytokines following CAR-T cell therapy for systemic hematologic malignancies [ 1 ]. A local inflammatory response occurring as an adverse effect of CAR-T cell therapy is a newly emerging concept [ 2 3 4 5 ]. Here, we describe the CT manifestations of local CRS (L-CRS) involving the head and neck.…”