APHON Pediatric Chemotherapy-Biotherapy Renewal

have been identified for the development of ICANS after CAR T-cell infusion, including the presence of B-ALL, high tumor burden, and a high CAR T-cell dose as well as younger age at time of infusion (Kennedy & Salama, 2020). There is also a correlation between cytokine release syndrome (CRS) and the development of ICANS. It has been found that patients with ICANS had CRS prior to the development of ICANS. Neurotoxicity after CAR T-cell infusion may arise from either the diffusion of cytokines into the central nervous system (high levels of IL-15, IL-6, IL-10, and IP-10 have been found in the serum of patients who develop ICANS) or the trafficking of CAR T cells into the central nervous system after CAR T-cell infusion. Tools for grading ICANS in pediatric patients and algorithms for treatment vary by institution; however, unlike with CRS, it has been found that neurotoxicity often does not respond to tocilizumab (Winter et al., 2020). Immune checkpoint inhibitors . Immune checkpoint inhibitors (ICPIs) modulate immune responses by attaching to immune receptors or ligands. ICPIs were developed to overcome the immune escape mechanisms of cancer progression and metastatic cancer dissemination (Tian et al., 2020). Immune checkpoint inhibitors are monoclonal antibodies that target cytotoxic T lymphocyte–associated antigen 4 (CTLA4), programmed death-1 receptor (PD-1), and programmed death ligand 1 (PD-L1), all of which have been implicated in the evasion of tumor cells from the surveillance of the body’s own immune system. Escaping immune system surveillance thereby allows the proliferation and dissemination of the cancerous cells (see Figure 5 ).