Consequences of hemophagocytic lymphohistiocytosis-like cytokine release syndrome toxicities and concurrent bacteremia

Pediatr Blood Cancer. 2021 Oct;68(10):e29247. doi: 10.1002/pbc.29247. Epub 2021 Jul 26.

Abstract

Serious bacterial infections (SBI) can lead to devastating complications with CD19 CAR T cells and cytokine release syndrome (CRS). Little is known about consequences of and risk factors for SBI with novel CAR T-cell constructs or with CRS complicated by HLH-like toxicities. We report on three patients with B-cell acute lymphoblastic leukemia treated with CD22 CAR T cells who developed SBI and CRS-associated HLH. Serum cytokine profiling revealed sustained elevations well beyond CRS resolution, suggesting ongoing systemic inflammation. Heightened inflammatory states converging with SBI contribute to poor outcomes, and recognition and prevention of extended inflammation may be needed to improve outcomes.

Trial registration: ClinicalTrials.gov NCT02315612.

Keywords: ALL molecular diagnosis and therapy; ALL relapse; clinical trials; cytokines; immunotherapy; infections.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antigens, CD19
  • Bacteremia* / immunology
  • Bacteremia* / microbiology
  • Cytokine Release Syndrome* / immunology
  • Humans
  • Immunotherapy, Adoptive
  • Lymphohistiocytosis, Hemophagocytic* / immunology
  • Lymphohistiocytosis, Hemophagocytic* / microbiology
  • Receptors, Chimeric Antigen
  • T-Lymphocytes

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen

Associated data

  • ClinicalTrials.gov/NCT02315612