Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T -Cell (CAR -T) Therapy for Diffuse Large B -Cell Lymphoma
Acute Kidney Injury and Electrolyte Abnormalities After Chimeric Antigen Receptor T -Cell (CAR -T) Therapy for Diffuse Large B -Cell Lymphoma
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DOI：
10.1053/j.ajkd.2019.10.011
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发表时间：
2020-07-01
影响因子：
13.2
通讯作者：
Sise, Meghan E.
中科院分区：
文献类型：
--
作者：
Gupta, Shruti;Seethapathy, Harish;Sise, Meghan E.
细胞因子释放综合征是嵌合抗原受体T细胞（CAR-T）治疗的一种众所周知的并发症，可导致多器官功能障碍。然而，CAR-T疗法的肾毒性尚不清楚。我们旨在描述急性肾损伤（阿基）的发生、原因和结局，沿着电解质异常的发生，在接受CAR-T治疗的弥漫性大B细胞淋巴瘤成人患者中。研究设计病例系列。设置和患者我们回顾了78例接受CAR-T治疗的成人患者的病程，2017年10月至2019年2月期间，在2家主要癌症中心使用axicabtagene ciloleucel或tisagenlecleucel进行T治疗。从电子健康记录中获得基线人口统计学、共病、药物和实验室值。使用KDIGO（肾脏疾病：改善全球结局）标准定义阿基。使用电子健康记录中包含的数据对CAR-T输注后前30天阿基事件和电解质异常的原因、临床过程和结局进行了表征。ResultsAmong 78例接受CAR-T治疗的患者中，85%发生了细胞因子释放综合征，其中62%接受了托珠单抗治疗。15例患者（19%）发生阿基：8例患者出现肾脏灌注减少，6例患者出现急性肾小管坏死，1例患者出现与疾病进展相关的尿路梗阻。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;低磷酸盐血症、低钾血症和低钠血症分别发生在75%、56%和51%的患者中。局限性样本量小;阿基通过回顾性图表审查裁定;缺乏活检数据。结论在接受CAR-T治疗的弥漫性大B细胞淋巴瘤患者系列中，阿基和电解质异常通常发生在细胞因子释放综合征的背景下。
Rationale & ObjectiveCytokine 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 DesignCase series.Setting & ParticipantsWe 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.ResultsAmong 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.LimitationsSmall sample size; AKI adjudicated by retrospective chart review; lack of biopsy data.ConclusionsIn 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.