Department of Pediatric Nephrology, The University of Tennessee Health Science Center, Memphis, TN, USA.
Department of Pediatrics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Pediatr Nephrol. 2024 Aug;39(8):2495-2503. doi: 10.1007/s00467-024-06331-7. Epub 2024 Mar 20.
BACKGROUND: CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. However, its use may be related to complications such as immune-mediated complications, infections, and end-organ dysfunction. The incidence of post-CAR T-cell therapy acute kidney injury (AKI) in the children, adolescent, and young adult (CAYA) patient population is largely unreported. METHODS: The objectives of this study were to determine the incidence of AKI in CAYA patients with high-risk B-cell malignancies treated with CD19-CAR T-cell therapy, evaluate potential risk factors for developing AKI, and determine patterns of kidney function recovery. We conducted a retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution. RESULTS: There was a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n = 7), with four cases being severe AKI (stages 2-3) and one patient requiring kidney replacement therapy. All episodes of AKI developed within the first 14 days after receiving CAR T-cell therapy and 50% of patients with AKI recovered kidney function to baseline within 30 days post-infusion. No evaluated pre-treatment risk factors were associated with the development of subsequent AKI; there was an association between AKI and cytokine release syndrome and neurotoxicity. We conclude that the risk of developing AKI following CD19-CAR T-cell therapy is highest early post-infusion, with most cases of AKI being severe. CONCLUSIONS: Frequent monitoring to facilitate early recognition and subsequent management of kidney complications after CD19-CAR T-cell therapy may reduce the severity of AKI in the CAYA patient population.
背景:CD19 特异性嵌合抗原受体 (CAR) T 细胞疗法已显示出在高危 B 细胞恶性肿瘤患者中具有良好的疾病反应。然而,其使用可能与免疫介导的并发症、感染和终末器官功能障碍等并发症有关。在儿童、青少年和年轻成人 (CAYA) 患者群体中,CAR T 细胞治疗后发生急性肾损伤 (AKI) 的发生率在很大程度上尚未报道。
方法:本研究的目的是确定接受 CD19-CAR T 细胞治疗的高危 B 细胞恶性肿瘤 CAYA 患者中 AKI 的发生率,评估发生 AKI 的潜在危险因素,并确定肾功能恢复的模式。我们对一家机构治疗的 34 名接受 CD19-CAR T 细胞治疗的 CAYA 患者进行了回顾性分析。
结果:输注后 30 天内任何级别 AKI 的累积发生率为 20%(n=7),其中 4 例为严重 AKI(2-3 期),1 例患者需要肾脏替代治疗。所有 AKI 均发生在接受 CAR T 细胞治疗后的前 14 天内,50%的 AKI 患者在输注后 30 天内恢复到基线肾功能。没有评估的治疗前危险因素与随后 AKI 的发生有关;AKI 与细胞因子释放综合征和神经毒性有关。我们得出结论,在接受 CD19-CAR T 细胞治疗后,AKI 的发生风险在输注后早期最高,大多数 AKI 为严重。
结论:在接受 CD19-CAR T 细胞治疗后,频繁监测以促进肾脏并发症的早期识别和后续管理,可能会降低 CAYA 患者群体中 AKI 的严重程度。
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