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DNT 细胞介导复发/难治性 B-ALL 患儿对 CAR-T 细胞治疗的耐药

英文原题:DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

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DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

PubMed 2024/05/10(内容时间) Ann Hematol Q3 · IF 2.3(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法是治疗复发/难治性(R/R)B 细胞急性淋巴细胞白血病(B-ALL)的里程碑式进展,但部分患者治疗后未能达到完全缓解,相关机制尚未阐明。本研究报告一名 9 岁难治性 B-ALL 儿童,在第二次复发后接受三次自体 CD19 CAR-T 输注。CAR-T 细胞在外周血和骨髓中均扩增,但患者未达到完全缓解,提示对 CAR-T 治疗无应答。病因分析发现,外周血、骨髓及自体 CAR-T 产品中 CD4/CD8 双阴性 T(DNT)细胞数量显著增加。综上,这些发现提示 DNT 细胞介导了该 R/R B-ALL 儿童患者对 CAR-T 治疗的耐药。

展开英文摘要原文

Chimeric antigen receptor T (CAR-T) cells therapy is a milestone achievement in the immunotherapy of relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL).

However, some patients treated with CAR-T cells do not achieve complete remission, the mechanisms of which have not been elucidated. In the present study, we report a 9-year-old pediatric patient with refractory B-ALL received a triple infusion of autologous CD19 CAR-T cells therapy after the second relapse. CAR-T cells expanded in the peripheral blood and bone marrow.

However, the patient did not achieve complete remission, indicating a lack of response to CAR-T cells therapy. Analysis of etiological factors revealed that the number of CD4 and CD8 double-negative T (DNT) cells was significantly upregulated in the peripheral blood, bone marrow, and autologous CAR-T cells products.

In conclusiont, these findings indicate that DNT cells mediated resistance to CAR-T cells therapy in this pediatric patient with R/R B-ALL.

论文信息

作者
Chen R、Tao Q、Wu F、Zhai Z、Jiang Y、Xu C、Wang H
第一作者单位
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.China
通讯作者单位
Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China. wanghuiping2831@163.com.China
文献类型
病例报告
期刊
Annals of hematology2024 Jul
原文标识
PubMed 38724656 · DOI 10.1007/s00277-024-05790-0