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病例报告:一名73岁诊断为难治性急性髓系白血病患者成功接受CLL1嵌合抗原受体T细胞(CAR-T)疗法与造血干细胞移植联合治疗

Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.

作者信息

Zhao Yifan, Wang Hao, Zhang Yu, Zhang Yi, Zhang Xiaomei, Zhao Mohan, Liu Jile, Guo Shujing, Zhao Mingfeng

机构信息

The First Central Clinical College of Tianjin Medical University, Tianjin, China.

Department of Intensive Care Medicine, Tianjin Hospital, Tianjin, China.

出版信息

Front Immunol. 2024 Sep 17;15:1454614. doi: 10.3389/fimmu.2024.1454614. eCollection 2024.

Abstract

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

摘要

急性髓系白血病(AML)的发病率随年龄增长而增加,老年患者的预后明显比年轻患者差。尽管维奈克拉与低甲基化药物的联合治疗已证明在无法耐受强化化疗的患者中预后有所改善,但对于那些未能通过当前治疗方案实现缓解的患者而言,仍存在治疗空白。在此,我们报告了自体CLL1嵌合抗原受体T细胞(CAR-T)疗法联合造血干细胞移植在一名73岁诊断为难治性AML患者中的成功临床应用。该患者在接受CLL1 CAR-T治疗后实现了形态学完全缓解(CR),骨髓恢复不完全且存在轻微微量残留病(MRD)。为进一步加强治疗并促进造血恢复,我们在输注CLL1 CAR-T细胞20天后进行了桥接异基因造血干细胞移植(allo-HSCT)。患者在HSCT治疗后实现了MRD阴性的CR。在11个月的随访期内,其原发性疾病维持完全缓解状态。该患者在输注CAR-T细胞后出现了2级细胞因子释放综合征和4级粒细胞减少症,而在allo-HSCT后观察到了几轮感染和移植物抗宿主病。尽管如此,通过全面提供支持性治疗,所有这些问题均得到了成功解决。我们成功证明了一种涉及CLL1 CAR-T疗法和allo-HSCT的高效且安全的联合策略,该策略表现出了显著的耐受性,即使对于老年AML患者也极具前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68d5/11442223/040915ea6728/fimmu-15-1454614-g001.jpg

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