There is evidence of systemic inflammation and endothelial dysfunction contributing to ICANS, and these included evidence that blood-brain barrier disruption, mediated by elevated levels of systemic and CNS-specific cytokines such as interferon-gamma, interleukin-6, and − 8 [42], as well as elevated levels of astrocyte-specific markers in cerebrospinal fluid [43]. This evidence concerns the gene IL6 and endothelial dysfunction.