Division of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA.
Renal Division, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA.
Am J Kidney Dis. 2020 Jul;76(1):63-71. doi: 10.1053/j.ajkd.2019.10.011. Epub 2020 Jan 20.
RATIONALE & OBJECTIVE: Cytokine release syndrome is a well-known complication of chimeric antigen receptor T-cell (CAR-T) therapy and can lead to multiorgan dysfunction. However, the nephrotoxicity of CAR-T therapy is unknown. We aimed to characterize the occurrence, cause, and outcomes of acute kidney injury (AKI), along with the occurrence of electrolyte abnormalities, among adults with diffuse large B-cell lymphoma receiving CAR-T therapy. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We reviewed the course of 78 adults receiving CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel at 2 major cancer centers between October 2017 and February 2019. Baseline demographics, comorbid conditions, medications, and laboratory values were obtained from electronic health records. AKI was defined using KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The cause, clinical course, and outcome of AKI events and electrolyte abnormalities in the first 30 days after CAR-T infusion were characterized using data contained in electronic health records. RESULTS: Among 78 patients receiving CAR-T therapy, cytokine release syndrome occurred in 85%, of whom 62% were treated with tocilizumab. AKI occurred in 15 patients (19%): 8 had decreased kidney perfusion, 6 developed acute tubular necrosis, and 1 patient had urinary obstruction related to disease progression. Those with acute tubular necrosis and obstruction had the longest lengths of stay and highest 60-day mortality. Electrolyte abnormalities were common; hypophosphatemia, hypokalemia, and hyponatremia occurred in 75%, 56%, and 51% of patients, respectively. LIMITATIONS: Small sample size; AKI adjudicated by retrospective chart review; lack of biopsy data. CONCLUSIONS: In this case series of patients with diffuse large B-cell lymphoma receiving CAR-T therapy, AKI and electrolyte abnormalities occurred commonly in the context of cytokine release syndrome.
背景与目的:细胞因子释放综合征是嵌合抗原受体 T 细胞(CAR-T)治疗的一种已知并发症,可导致多器官功能障碍。然而,CAR-T 治疗的肾毒性尚不清楚。我们旨在描述接受 CAR-T 治疗的弥漫性大 B 细胞淋巴瘤成人患者中急性肾损伤(AKI)的发生、原因和结局,以及电解质异常的发生情况。 研究设计:病例系列。 研究场所和参与者:我们回顾了 2017 年 10 月至 2019 年 2 月期间在 2 个主要癌症中心接受 axicabtagene ciloleucel 或 tisagenlecleucel 治疗的 78 名接受 CAR-T 治疗的成年人的治疗过程。从电子病历中获取基线人口统计学、合并症、药物和实验室值。根据 KDIGO(肾脏疾病:改善全球结局)标准定义 AKI。使用电子病历中包含的数据,描述 CAR-T 输注后 30 天内 AKI 事件和电解质异常的原因、临床过程和结局。 结果:在接受 CAR-T 治疗的 78 名患者中,细胞因子释放综合征发生在 85%的患者中,其中 62%接受了托珠单抗治疗。15 名患者(19%)发生 AKI:8 名患者存在肾脏灌注减少,6 名患者发生急性肾小管坏死,1 名患者因疾病进展出现尿路梗阻。发生急性肾小管坏死和梗阻的患者住院时间最长,60 天死亡率最高。电解质异常很常见;分别有 75%、56%和 51%的患者出现低磷血症、低钾血症和低钠血症。 局限性:样本量小;AKI 通过回顾性图表审查进行判定;缺乏活检数据。 结论:在这项接受 CAR-T 治疗的弥漫性大 B 细胞淋巴瘤患者的病例系列研究中,细胞因子释放综合征背景下常发生 AKI 和电解质异常。
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