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儿童、青少年和年轻成人 B 细胞急性淋巴细胞白血病患者接受 CD19 特异性嵌合抗原受体 T 细胞治疗后的急性肾损伤。

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.

机构信息

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.

出版信息

Pediatr Nephrol. 2024 Aug;39(8):2495-2503. doi: 10.1007/s00467-024-06331-7. Epub 2024 Mar 20.


DOI:10.1007/s00467-024-06331-7
PMID:38507119
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11199105/
Abstract

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.

摘要

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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引用本文的文献

[1]
The Role of miRNAs as Predictors of Acute Lymphoblastic Leukemia Chemotherapy Toxicity in Children: A Systematic Review.

J Clin Med. 2025-8-20

[2]
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Pediatr Nephrol. 2025-7-7

[3]
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[4]
Acute kidney injury following CAR-T cell therapy: a nephrologist's perspective.

Clin Kidney J. 2024-11-15

[5]
Acute kidney injury in hematological patients treated with CAR-T cells: risk factors, clinical presentation and impact on outcomes.

Sci Rep. 2024-11-6

[6]
EASIX and m-EASIX predict CRS and ICANS in pediatric and AYA patients after CD19-CAR T-cell therapy.

Blood Adv. 2025-1-28

本文引用的文献

[1]
Higher doses of tisagenlecleucel are associated with improved outcomes: a report from the pediatric real-world CAR consortium.

Blood Adv. 2023-2-28

[2]
Mortality of Hemato-Oncologic Patients Admitted to a Pediatric Intensive Care Unit: A Single-Center Experience.

Front Pediatr. 2022-7-12

[3]
Incidence and Risk Factors for Acute Kidney Injury After Chimeric Antigen Receptor T-Cell Therapy.

Mayo Clin Proc. 2022-7

[4]
Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies.

Hematol Oncol Clin North Am. 2022-8

[5]
Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL.

Blood Adv. 2022-11-8

[6]
Acute kidney injury in pediatric hematopoietic cell transplantation: critical appraisal and consensus.

Pediatr Nephrol. 2022-6

[7]
Management of adults and children receiving CAR T-cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA).

Ann Oncol. 2022-3

[8]
Assessment of kidney function: clinical indications for measured GFR.

Clin Kidney J. 2021-2-22

[9]
Harmonizing acute and chronic kidney disease definition and classification: report of a Kidney Disease: Improving Global Outcomes (KDIGO) Consensus Conference.

Kidney Int. 2021-9

[10]
Systematic Review of Risk factors and Incidence of Acute Kidney Injury Among Patients Treated with CAR-T Cell Therapies.

Kidney Int Rep. 2021-2-17

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