Double systemic cytokine release syndrome following sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells after autologous hematopoietic stem cell transplantation for a central diffuse large B-cell lymphoma patient: A case report and literature review

Front Immunol. 2023 Jan 31:14:1098815. doi: 10.3389/fimmu.2023.1098815. eCollection 2023.

Abstract

Background: Chimeric Antigen Receptor T cell(CAR T-cell) therapy has been a great success in relapsed/refractory acute B lymphoblastic leukemia and B-cell lymphoma. At the same time, there are also related adverse reactions, especially cytokine release syndrome(CRS) and immune effector cell associated neurotoxicity syndrome(ICANS). However, Double CRS caused by CRA T cells are very rare.

Case report: Here, we report a 33-year-male with secondary central diffuse large B-cell lymphoma(CNSL) who develpoed double CRS following sequential infusion of Anti-CD22 and Anti-CD19 CAR T cells after autologous hematopoietic stem cell transplantation(ASCT). On d+5, the patient developed high fever, along with chilly sensation, shivering, headache, blood oxygen desaturation, shock, weakness, severe thirst, and heart rate decline. IL-6 and ferritin increased significantly. The patient was diagnosed with the first CRS (grade 3). On d+36, the patient again had a persistent fever(T>39C) and limbs rash. IL-6 and ferritin again increased significantly on d+38. After exclusion of infection, a diagnosis of double CRS was made. The patient's symptoms were completely relieved after receiving tocilizumab, glucocorticoids, and other supportive treatments on d+45.On d+90, contrast-enhanced MR angiogram shows that the lesion basically disappeared, indicating the patient had achieved CR. At the end of the follow-up at d+150, the patient was functioning normally without any sequelae.

Conclusion: This is the first reported case worldwide where the patient with secondary CNSL suffered double CRS after CAR T-cell infusion. Our findings showed that it is important to increase awareness of early detection and diagnosis of double CRS and adopt appropriate treatment strategies.

Keywords: adverse reactions; central diffuse large B-cell lymphoma; chimeric antigen receptor T cell; cytokine release syndrome; immunotherapy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Antigens, CD19
  • Cytokine Release Syndrome / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Interleukin-6
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Male
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes

Substances

  • Antigens, CD19
  • Interleukin-6
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen