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供者 CD7 CAR-T 细胞桥接异基因造血干细胞移植治疗 T 细胞血液恶性肿瘤

英文原题:Donor CD7 Chimeric Antigen Receptor T Cell Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for T Cell Hematologic Malignancy.

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Donor CD7 Chimeric Antigen Receptor T Cell Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for T Cell Hematologic Malignancy.

PubMed 2022/11/24(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

对于造血重建而言,快速桥接至异基因造血干细胞移植(allo-HSCT)至关重要。本文报告了供者CD7嵌合抗原受体(CAR)T细胞疗法(CAR-T)桥接allo-HSCT治疗12例复发/难治性(r/r)T-ALL或T细胞淋巴母细胞淋巴瘤(T-LBL)患者的疗效和安全性。从CAR-T 输注至allo-HSCT的中位时间为33.5天(范围,30至55天)。采用减低强度预处理,除1例患者外,所有患者均成功植入。平均随访301天(范围,238至351天),其余11例患者在末次随访时均存活且无病。3例患者观察到急性移植物抗宿主病(GVHD),3例患者发生慢性GVHD,均为局限型。在当前方案下,感染是移植后的主要并发症,除1例患者外,所有感染均得到良好控制,该患者因感染诱导的炎性细胞因子风暴导致的多器官衰竭于移植后第14天死亡。1例患者复发(CD7+),3例患者转为微小残留病(MRD)阳性(1例CD7+,1例CD7-,1例仅融合基因阳性)。随后,这3例患者均通过CD7 CAR-T 再输注或停用免疫抑制剂达到MRD阴性完全缓解。

我们的研究首次表明,供者CD7 CAR-T 桥接allo-HSCT这一新策略在改善r/r T-ALL或T-LBL患者的无病生存期方面具有高度有效性和可行性。

展开英文摘要原文

It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution.

Here we report on the efficacy and safety of donor CD7 chimeric antigen receptor (CAR) T cell therapy (CAR-T) bridging to allo-HSCT in treating 12 patients with relapsed/refractory (r/r) T-ALL or T-cell lymphoblastic lymphoma (T-LBL). The median time from CAR-T infusion to allo-HSCT was 33. 5 days (range, 30 to 55 days). With reduced-intensity conditioning, all patients except 1 successfully engrafted. With a mean follow-up of 301 days (range, 238 to 351 days), the remaining 11 patients were alive and disease-free at their last follow-up. Acute graft-versus-host disease (GVHD) was observed in 3 patients, and chronic GVHD developed in 3 patients, all with a limited pattern.

Under the current protocol, infection was the main complication post-transplantation, and all infections were well controlled except in 1 patient, who died of multiple organ failure caused by an infection-induced inflammatory cytokine storm at days 14 post-transplantation.

One patient relapsed (CD7 + ), and 3 patients became minimal residual disease (MRD) positive (CD7 + in 1, CD7 - in 1, fusion gene positive only in 1). Subsequently, all 3 of these patients achieved an MRD-negative complete remission with either CD7 CAR-T reinfusion or immunosuppressive agent withdrawal.

Our study shows for the first time that a novel strategy of donor CD7 CAR-T bridging to allo-HSCT can be highly effective and feasible in improving disease-free survival for patients with r/r T-ALL or T-LBL.

论文信息

作者
Li Z、An N、Yang K、Meng F、Xu T、Peng X、Wen X、Li J
第一作者单位
Department of Bone Marrow Transplantation, Beijing Boren Hospital, Beijing 100070, China.China
通讯作者单位
Department of Bone Marrow Transplantation, Beijing Boren Hospital, Beijing 100070, China. Electronic address: wut@gobroadhealthcare.com.China
期刊
Transplantation and cellular therapy2023 Mar
原文标识
PubMed 36427783 · DOI 10.1016/j.jtct.2022.11.013