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CD19+ 谱系嵌合状态:既往接受造血干细胞移植患者抗 CD19 CAR-T 细胞治疗后的早期生物标志物

英文原题:CD19+ lineage chimerism, an early biomarker after anti-CD19 CAR-T cell therapy in patients previously receiving a hematopoietic stem cell transplantation.

查看英文原题

CD19+ lineage chimerism, an early biomarker after anti-CD19 CAR-T cell therapy in patients previously receiving a hematopoietic stem cell transplantation.

PubMed 2022/08/08(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

T细胞表达嵌合抗原受体靶向CD19的治疗(抗CD19 CAR-T)为复发/难治性B细胞急性淋巴细胞白血病(B-ALL)的管理和治疗带来了突破。输注后,通常通过骨髓微小残留病阴性以及外周血CD19阳性B淋巴细胞缺失(B细胞缺失)监测抗CD19 CAR-T 疗效。对于接受抗CD19 CAR-T 前曾进行异基因造血干细胞移植(HSCT)的患者,监测谱系特异性嵌合状态可能具有帮助。研究观察了4例HSCT后接受抗CD19 CAR-T 并早期达到完全缓解的患者。采用分子技术监测时,CD19阳性谱系的混合嵌合早于流式细胞术检测到的B细胞缺失出现;而CD3阳性谱系混合嵌合并未呈现这种提前变化。CD19阳性谱系的混合嵌合可先于抗CD19 CAR-T 疗效丧失和白血病复发出现。供者淋巴细胞输注(DLI)未能阻止复发,但恢复了CD3阳性谱系的完全供者嵌合。

我们建议,对HSCT后接受抗CD19 CAR-T 并获得完全缓解的患者常规持续开展谱系嵌合分析,因为这有助于及早采取治疗干预。

不过,DLI在这一情境中的作用尚不明确,仍需开展进一步的前瞻性研究。

展开英文摘要原文

Treatment targeting CD19 by a chimeric antigen receptor expressed on T cells (anti-CD19 CAR-T) has led to a breakthrough in the management and treatment of relapsed and refractory B- cell acute lymphoblastic leukemia (B-ALL).

After infusion, the efficacy of anti-CD19 CAR-T is monitored by bone marrow negative minimal residual disease and the absence of peripheral CD19 + B lymphocytes (B-cell aplasia). In patients who have received an allogenic Hematopoietic Stem Cell Transplantation (HSCT) prior to treatment with anti-CD19 CAR-T, monitoring lineage-specific chimerism could be helpful.

We found that on 4 patients who received anti-CD19 CAR-T cells after HSCT and achieved early complete response, CD19 + lineage mixed chimerism but not CD3 + lineage mixed chimerism monitored by molecular techniques anticipated earlier than B-cell aplasia determined by flow cytometry, lack of effectiveness of anti-CD19 CAR-T and leukemia relapse. Donor lymphocyte infusions (DLIs) did not prevent relapse but recovered CD3 + full donor chimerism.

We suggest that continuous lineage chimerism analysis should be done routinely in patients who receive anti-CD19 CAR-T cells after HSCT and achieve complete remission because it can support early treatment intervention.

However, the role of DLI in this setting is unclear, so further prospective studies should be developed.

论文信息

作者
Martínez-Romera I、Galán-Gómez V、González-Martínez B、Guerra García P、San Román Pacheco S、Corral Sánchez D、Mozo Del Castillo Y、Bueno Sánchez D
单位
Pediatric Hematology and Oncology Department, La Paz University Hospital, Madrid, Spain.Spain
期刊
Frontiers in immunology2022
原文标识
PubMed 36003375 · DOI 10.3389/fimmu.2022.960412