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B 细胞急性淋巴细胞白血病儿童、青少年和年轻成人患者 CD19 特异性 CAR-T 细胞治疗后的急性肾损伤

英文原题:Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia.

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Acute kidney injury following treatment with CD19-specific CAR T-cell therapy in children, adolescent, and young adult patients with B-cell acute lymphoblastic leukemia.

PubMed 2024/03/20(内容时间) Pediatr Nephrol Q1 · IF 2.5(JCR 2025)

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研究概要

在 CAYA 患者群体中,频繁监测以促进 CD19-CAR-T 细胞治疗后肾脏并发症的早期识别和后续管理,可能降低 AKI 的严重程度。

研究思路结论见上方概要

CD19特异性嵌合抗原受体(CAR)T细胞疗法在高危B细胞恶性肿瘤患者中已显示出有前景的疾病缓解。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相关。在儿童、青少年和年轻成人(CAYA)患者群体中,CAR-T 细胞治疗后急性肾损伤(AKI)的发生率在很大程度上尚未被报道。

本研究的目的在于确定接受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,并确定肾功能恢复模式。我们对在单一机构接受CD19-CAR-T 细胞治疗的34例CAYA患者进行了回顾性分析。

输注后30天内任何级别AKI的累积发生率为20%(n=7),其中4例为重度AKI(2-3期),1例患者需要肾脏替代治疗。所有AKI发作均发生在接受CAR-T 细胞治疗后的前14天内,50%的AKI患者在输注后30天内肾功能恢复至基线水平。未发现所评估的治疗前危险因素与后续AKI的发生相关;AKI与细胞因子释放综合征和神经毒性之间存在关联。我们得出结论,CD19-CAR-T 细胞治疗后发生AKI的风险在输注后早期最高,且大多数AKI病例为重度。

展开英文摘要原文

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.

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.

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.

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.

论文信息

作者
Petgrave Y、Selukar S、Epperly R、Naik S、Santos ND、Triplett BM、Gottschalk S、Bissler J
第一作者单位
Department of Pediatric Nephrology, The University of Tennessee Health Science Center, Memphis, TN, USA.United States
通讯作者单位
Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN, USA. Aimee.Talleur@stjude.org.United States
期刊
Pediatric nephrology (Berlin, Germany)2024 Aug
原文标识
PubMed 38507119 · DOI 10.1007/s00467-024-06331-7