本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2313812

摘要内容如下：

背景

复发或难治的血液系统癌症患者预后不良。嵌合抗原受体（CAR）T细胞疗法作为异基因造血干细胞移植（HSCT）的桥梁，具有长期消除肿瘤的潜力。然而，HSCT前骨髓消融术和移植物抗宿主病（GVHD）预防剂具有毒性作用，可清除残留的CAR T细胞并损害抗肿瘤作用。CAR T细胞疗法和异基因造血干细胞移植的整合是否可以保留CAR T细胞功能并改善肿瘤控制尚不清楚。

方法

我们在10例复发或难治性CD7阳性白血病或淋巴瘤患者中测试了一种新的“一体化”策略，包括序贯CD7 CAR T细胞治疗和单倍体相合造血干细胞移植。在CAR T细胞治疗导致血液学不完全恢复的完全缓解后，患者接受单倍体相合HSCT，而不进行药物骨髓消融或GVHD预防药物。密切监测毒性作用和疗效。

结果

CAR T细胞治疗后，所有10名患者均完全缓解，血液学恢复不完全，全血细胞减少4级。单倍体相合造血干细胞移植后，1例患者在第13天死于感染性休克和脑炎，8例患者为完全供者嵌合体，1例患者为自体造血。3例患者出现2级HSCT相关急性GVHD。CAR T细胞治疗后的中位随访时间为15.1个月（3.1至24.0个月）。6名患者仍处于微小残留病阴性完全缓解，2名患者CD7阴性白血病复发，1名患者在3.7个月时死于感染性休克。估计的1年总生存率为68%（95%可信区间[CI]，43-100），估计的1年无病生存率为54%（95%CI，29-100）。

结论

我们的研究结果表明，序贯CD7 CAR T细胞治疗和单倍体相合HSCT是安全有效的，可缓解和发生严重但可逆的不良事件。这一策略为不适合常规异基因造血干细胞移植的CD7阳性肿瘤患者提供了一种可行的方法。（国家自然科学基金和浙江省科技厅重点项目资助；ClinicalTrials.gov，NCT04599556和NCT04538599）。

英文原文如下：

Abstracts

BACKGROUND  Patients with relapsed or refractory hematologic cancers have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapy as a bridge to allogeneic hematopoietic stem-cell transplantation (HSCT) has the potential for long-term tumor elimination. However, pre-HSCT myeloablation and graft-versus-host disease (GVHD) prophylaxis agents have toxic effects and could eradicate residual CAR T cells and compromise antitumor effects. Whether the integration of CAR T-cell therapy and allogeneic HSCT can preserve CAR T-cell function and improve tumor control is unclear.

METHODS  We tested a novel "all-in-one" strategy consisting of sequential CD7 CAR T-cell therapy and haploidentical HSCT in 10 patients with relapsed or refractory CD7-positive leukemia or lymphoma. After CAR T-cell therapy led to complete remission with incomplete hematologic recovery, patients received haploidentical HSCT without pharmacologic myeloablation or GVHD prophylaxis drugs. Toxic effects and efficacy were closely monitored.

RESULTS  After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis. Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission, 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months. The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100).

CONCLUSIONS  Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT. (Funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province; ClinicalTrials.gov numbers, NCT04599556 and NCT04538599.).

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