Cancer immunotherapy: Adoptive cell therapies, cytokine-related toxicities, and the kidneys

Abstract

Adoptive cell therapies represent a new frontier in the quest for potent, personalized therapies for malignant disease with fewer of the widespread adverse events associated with standard chemotherapy. Adoptive cell therapies involve the identification, isolation, and expansion (with or without genetic manipulation) and then transfer of T cells with specific antitumor activity into patients with malignant disease to activate an effective antitumor immune response. These therapies include the tumor infiltrating lymphocytes, T-cell receptors, and chimeric antigen receptor T cells. These therapies are associated with unique, potentially devastating but usually reversible toxicities related to supraphysiologic cytokine activation, including cytokine release syndrome, chimeric antigen receptor T-cell-related encephalopathy syndrome, and hemophagocytic lymphohistiocytosis; tumor lysis syndrome is uncommon but can occur in patients with large disease burdens. Prompt, vigilant, and aggressive supportive care with a multidisciplinary approach is imperative to treat the toxicities associated with the adoptive cell therapies. From a renal standpoint, adoptive cell therapy has been associated with varying degrees of acute kidney injury, ranging from mild increases in creatinine to renal failure requiring renal replacement therapy. Renal injury may be related to significant intravascular volume shifts in the setting of cytokine-related vasodilation. This review aims to familiarize nephrologists with these relatively new therapies and their associated toxicities.

Long‐term nephrotoxicity in irradiated pediatric kidney tumor survivors: A systematic review

“…Low mitotic rates of normal kidney tissue associates with delayed expression of kidney injury after RT. 40,43 Early changes of microvascular injury are followed by parenchymal damage leading to kidney mass reduction and finally fibrosis. 44,45 Whether the radiosensitivity of the kidneys in children is comparable to adults, and/or the radiation constraints can be extrapolated to the still growing pediatric population is not well known, although it is conceivable since the number of nephrons we are born with is fixed and does not increase during the infancy period.…”

“…Long‐term follow‐up of the patients at risk is required since radiation kidney damage can occur as a late event, usually presenting months or years after the radiation exposure. Low mitotic rates of normal kidney tissue associates with delayed expression of kidney injury after RT 40,43 . Early changes of microvascular injury are followed by parenchymal damage leading to kidney mass reduction and finally fibrosis 44,45 .…”

A Case of Spontaneous Tumor Lysis After Pathologic Femur Fracture in Squamous Cell Lung Cancer

“…It is even more uncommon for TLS to occur spontaneously in non-hematologic solid tumors. 2 - 5 Here, we present a case of spontaneous TLS in metastatic squamous cell carcinoma of the lung.…”