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嵌合抗原受体T细胞(CAR-T)疗法后进行异基因造血干细胞移植,在Ph样急性淋巴细胞白血病(ALL)和其他高危ALL之间产生了相当的结果。

CAR-T cell therapy followed by allogenic hematopoietic stem cell transplantation yielded comparable outcome between Ph like ALL and other high-risk ALL.

作者信息

Dai Hai-Ping, Kong Dan-Qing, Shen Hong-Jie, Cui Wei, Wang Qian, Li Zheng, Yin Jia, Kang Li-Qing, Yu Lei, Wu De-Pei, Tang Xiao-Wen

机构信息

The First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Suzhou, 215006, China.

Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.

出版信息

Biomark Res. 2023 Feb 15;11(1):19. doi: 10.1186/s40364-023-00451-2.

Abstract

It was previously believed that patients with Ph-like ALL had poorer prognosis compared with other B-ALL subgroups due to resistance to conventional chemotherapy and lack of targeted drugs. CAR-T therapy has been successfully applied in the treatment of relapsed and refractory B-ALL. Currently, there are few data on whether CAR-T therapy can alter the outcome of Ph-like ALL. Here we included 17 Ph-like, 23 Ph+ and 51 other B-ALL patients, who received autologous CAR T-cell therapy and subsequently allogenic stem cell transplantation. Patients in the Ph-like group and B-ALL-others group were younger that those in the Ph+ group (P=0.001). Ph-like and Ph+ ALL patients showed higher white blood cell counts at diagnosis (P=0.025). The percentage of patients with active disease before receiving CAR T-cells infusion was 64.7%, 39.1% and 62.7% in the Ph-like, Ph+ and B-ALL-others groups. The response rates to CAR-T therapy were 94.1% (16/17), 95.6% (22/23) and 98.0% (50/51) in the Ph-like, Ph+ and B-ALL-others groups. Measurable residual disease negative CR was achieved in 64.7% (11/17), 60.9% (14/23) and 54.9% (28/51) in the Ph-like, Ph+ and B-ALL-others groups, respectively. The estimated rates of 3-year overall survival (65.9%±16.5%, 59.7%±10.5% and 61.6%±7.3%, P=0.758) and 3-year relapse-free survival (59.8%±14.8%, 63.1%±10.5% and 56.3%±7.1%, P=0.764) were comparable among the Ph-like, Ph+ and B-ALL-others groups. Estimated 3-year cumulative relapse rate was 7.8%±0.6%, 23.4%±0.9% and 29.0%±0.4% (P=0.241). Our findings suggest that CART followed by allo-HSCT results in a comparable prognosis in Ph-like ALL and other high-risk B-ALL.Trial registration ClinicalTrials. gov, NCT03275493, Registered on September 7, 2017, prospectively registered and NCT03614858, Registered on August 3, 2018, prospectively registered.

摘要

以前人们认为,与其他B-ALL亚组相比,Ph样ALL患者的预后较差,原因是对传统化疗耐药且缺乏靶向药物。CAR-T疗法已成功应用于复发和难治性B-ALL的治疗。目前,关于CAR-T疗法是否能改变Ph样ALL的治疗结果的数据很少。在此,我们纳入了17例Ph样、23例Ph+和51例其他B-ALL患者,他们接受了自体CAR T细胞治疗,随后进行了异基因干细胞移植。Ph样组和B-ALL其他组的患者比Ph+组的患者年轻(P=0.001)。Ph样和Ph+ ALL患者在诊断时白细胞计数较高(P=0.025)。在接受CAR T细胞输注前,Ph样组、Ph+组和B-ALL其他组中疾病活跃的患者百分比分别为64.7%、39.1%和62.7%。Ph样组、Ph+组和B-ALL其他组对CAR-T疗法的缓解率分别为94.1%(16/17)、95.6%(22/23)和98.0%(50/51)。Ph样组、Ph+组和B-ALL其他组分别有64.7%(11/17)、60.9%(14/23)和54.9%(28/51)的患者实现了微小残留病阴性的完全缓解。Ph样组、Ph+组和B-ALL其他组的3年总生存率估计值(分别为65.9%±16.5%、59.7%±10.5%和61.6%±7.3%,P=0.758)和3年无复发生存率估计值(分别为59.8%±14.8%、63.1%±10.5%和56.3%±7.1%,P=0.764)相当。估计的3年累积复发率分别为7.8%±0.6%、23.4%±0.9%和29.0%±0.4%(P=0.241)。我们的研究结果表明,CAR-T治疗后进行异基因造血干细胞移植,Ph样ALL和其他高危B-ALL的预后相当。试验注册ClinicalTrials.gov,NCT03275493,于2017年9月7日注册,前瞻性注册;NCT03614858,于2018年8月3日注册,前瞻性注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1a6/9930301/d60661e1857e/40364_2023_451_Fig1_HTML.jpg

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