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在嵌合抗原受体T细胞疗法后,一名复发/难治性多发性骨髓瘤患者未进行预处理方案的成功单倍体相合移植。

A successful haploidentical transplantation without conditioning regimen for a relapsed/refractory multiple myeloma patient after chimeric antigen receptor T-cell therapy.

作者信息

Dai Zigang, Yu Nanzhou, Cao Yang, Zhou Jianfeng, Zhang Yicheng, Wang Na, Zhou Xiaoxi

机构信息

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

出版信息

Cytotherapy. 2025 Mar;27(3):295-299. doi: 10.1016/j.jcyt.2024.10.005. Epub 2024 Dec 16.

Abstract

BACKGROUND AIMS

With novel therapies improving prognosis, the complications of multiple myeloma after multi-line treatment, particularly myelosuppression, have become a crucial determinant of long-term outcomes. Non-myeloablative allogeneic hematopoietic stem cell transplantation is a feasible option, but the transplant-related mortality rate remains high. Our study presents a relapsed/refractory multiple myeloma patient with a 9-year disease history.

METHODS

The patient underwent multiple chemotherapy treatments and achieved partial remission. The patient then received two B-cell maturation antigen-targeting chimeric antigen receptor (CAR) T-cell treatments with lymphodepletion conditioning of fludarabine and cyclophosphamide.

RESULTS

At the fifth month after the second CAR T-cell treatment, the patient achieved complete remission but developed refractory myelosuppression (grade 4 according to Common Terminology Criteria for Adverse Events 5.0) after several severe infections. In order to facilitate hematopoietic recovery, her daughter's stem cells were infused into her, which fortunately implanted without conditioning. After thrombotic microangiopathy and acute graft-versus-host disease, the patient was discharged with consistent full donor chimerism. We assume this engraftment may be attributed to the patient's severe hematopoietic failure and further host lymphodepletion by fludarabine.

CONCLUSIONS

This study highlights the potential of allogeneic hematopoietic stem cell transplantation with reduced conditioning intensity or even the omission of conditioning, particularly for a relapsed/refractory multiple myeloma patient who struggles with severe myelosuppression after long-term treatment.

摘要

背景与目的

随着新型疗法改善预后,多线治疗后多发性骨髓瘤的并发症,尤其是骨髓抑制,已成为长期预后的关键决定因素。非清髓性异基因造血干细胞移植是一种可行的选择,但移植相关死亡率仍然很高。我们的研究介绍了一位有9年病史的复发/难治性多发性骨髓瘤患者。

方法

该患者接受了多次化疗并达到部分缓解。随后,患者接受了两次靶向B细胞成熟抗原的嵌合抗原受体(CAR)T细胞治疗,并采用氟达拉滨和环磷酰胺进行淋巴细胞清除预处理。

结果

在第二次CAR T细胞治疗后的第五个月,患者达到完全缓解,但在经历几次严重感染后出现难治性骨髓抑制(根据不良事件通用术语标准5.0为4级)。为促进造血恢复,将其女儿的干细胞输注给她,幸运的是,未进行预处理干细胞就成功植入。在出现血栓性微血管病和急性移植物抗宿主病后,患者出院时供体嵌合率持续完全。我们认为这种植入可能归因于患者严重的造血功能衰竭以及氟达拉滨进一步导致的宿主淋巴细胞清除。

结论

本研究强调了降低预处理强度甚至省略预处理的异基因造血干细胞移植的潜力,特别是对于长期治疗后出现严重骨髓抑制的复发/难治性多发性骨髓瘤患者。

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