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

IF 5.7 2区 医学 Q1 IMMUNOLOGY
Yifan Zhao, Hao Wang, Yu Zhang, Yi Zhang, Xiaomei Zhang, Mohan Zhao, Jile Liu, Shujing Guo, Mingfeng Zhao
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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.
病例报告:一位73岁的难治性急性髓性白血病患者成功接受了CLL1 CAR-T疗法和造血干细胞移植的联合治疗
急性髓性白血病(AML)的发病率随着年龄的增长而增加,老年患者的预后明显差于年轻患者。虽然venetoclax和低甲基化药物的联合疗法改善了无法耐受强化化疗患者的预后,但对于那些无法通过现有治疗方案获得缓解的患者来说,仍然存在治疗空白。在此,我们报告了自体CLL1 CAR-T疗法联合造血干细胞移植在一名73岁的难治性急性髓细胞白血病患者身上的成功临床应用。患者在接受CLL1 CAR-T治疗后获得了形态学上的完全缓解(CR),但骨髓未完全恢复,且存在轻微的最小残留病(MRD)。为了进一步加强治疗并促进造血功能的恢复,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)。造血干细胞移植治疗后,患者获得了MRD阴性的CR。在11个月的随访期间,他的原发病保持完全缓解状态。输注 CAR-T 细胞后,患者出现了 2 级细胞因子释放综合征和 4 级粒细胞减少症,异体造血干细胞移植后出现了数次感染和移植物抗宿主病。不过,通过全面的支持性治疗,所有这些问题都得到了成功解决。我们成功展示了一种高效、安全的联合策略,包括CLL1 CAR-T疗法和allo-HSCT,该策略具有显著的耐受性,即使对于老年急性髓细胞白血病患者也大有可为。
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来源期刊
CiteScore
9.80
自引率
11.00%
发文量
7153
审稿时长
14 weeks
期刊介绍: Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.
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