CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
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.
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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CD19特异性嵌合抗原受体(CAR)T细胞疗法已使高危B细胞恶性肿瘤患者获得良好疾病应答,但治疗也可能导致发病甚至死亡,主要与免疫介导并发症(细胞因子释放综合征[CRS]和神经毒性[NTX])、感染及终末器官功能障碍有关。尽管这些全身毒性已有充分描述,儿童、青少年和青年成人(CAYA)患者接受CAR-T 后发生急性肾损伤(AKI)的情况尚未得到充分报道。
本研究旨在确定接受CD19 CAR-T 的高危B细胞恶性肿瘤CAYA患者AKI发生率,评估潜在危险因素并描述肾功能恢复模式。本单中心回顾性分析纳入34名接受CD19 CAR-T 治疗的CAYA患者。截至输注后第30天,任何级别AKI的累积发生率为20%(n=7),其中4例为重度AKI(2至3期),1名患者需要肾脏替代治疗。所有AKI均发生在CAR-T 治疗后的前14天;发生AKI者中有50%在输注后30天内肾功能恢复至基线水平。研究评估的治疗前危险因素均未与后续AKI发生相关;AKI则与CRS和NTX有关。研究认为,CD19 CAR-T 后AKI风险在输注早期最高,且多数病例为重度。尽管本队列多数AKI患者肾功能有所恢复,但加强监测,以便及早识别并处理CAR-T 后的肾脏并发症,可能降低CAYA患者AKI严重程度。
CD19-specific chimeric antigen receptor (CAR) T-cell therapy has shown promising disease responses in patients with high-risk B-cell malignancies. Treatment with CD19-CAR T-cell therapy is also associated with the risk of morbidity and mortality, primarily related to immune-mediated complications (cytokine release syndrome [CRS] and neurotoxicity [NTX]), infections, and end-organ dysfunction. Despite these well-described systemic toxicities, 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.
In this retrospective analysis of 34 CAYA patients treated with CD19-CAR T-cell at a single institution, we found a cumulative incidence of any grade AKI by day 30 post-infusion of 20% (n=7), with 4 cases being severe AKI (Stage 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 CRS and NTX.
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. Although most patients with AKI in our cohort had recovery of kidney function, 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.
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