CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL

IF 3.6 3区医学 Q2 HEMATOLOGY

Transplantation and Cellular Therapy Pub Date : 2025-02-01 DOI:10.1016/j.jtct.2024.11.009

Zhihui Li , Qinlong Zheng , Keyan Yang , Teng Xu , Lei Wang , Xianxuan Wang , Wiaopei Wen , Jingjing Wang , Yongqiang Zhao , Yanzhi Song , Chen Chen , Qi Zhou , Tong Wu

{"title":"CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL","authors":"Zhihui Li , Qinlong Zheng , Keyan Yang , Teng Xu , Lei Wang , Xianxuan Wang , Wiaopei Wen , Jingjing Wang , Yongqiang Zhao , Yanzhi Song , Chen Chen , Qi Zhou , Tong Wu","doi":"10.1016/j.jtct.2024.11.009","DOIUrl":null,"url":null,"abstract":"<div><div>T-ALL is caused by abnormal proliferation of T cells. It comprises 25%-50% of ALL cases in children and adults. Outlook for R/R T-ALL/LBL and patients over 60 is even dimmer. The treatment is challenging due to its biological and genetic diversity, limiting the development of effective targeted and immunotherapeutic strategies. Salvaged allo-HSCT offers only 20% to 30% DFS. This current study retrospectively analyzed 90 patients with R/R T-ALL (40, 44.4%) or T-LBL (50, 55.6%) treated at Beijing Gobroad Boren Hospital from February 2018 to January 2023. The median age was 14 (range: 2–65) y old. Somatic and germline gene mutations were detected by sequencing pretransplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (CR group), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CAR-T before allo-HSCT (CART group) and the rest 17 patients in NR underwent salvaged transplant (NR group). The results indicate that CD7 CAR-T group have OS (<em>p</em> = .029; 2-y OS rates: 54.4% [95% CI: 38.9% to 76%]) and DFS (<em>p</em> = .00032; 2-y DFS: 51.0% (95% CI: 36.9% to 70.7%)) similar to those in the CR group, but better than those in the NR group. The CIR for CD7 CAR-T group and CR group was significantly lower than NR group after 1 y (<em>p</em> = .0016; CAR-T group 2-y CIR: 31.67% (95% CI: 19.3% to 49.2%)). Our study examined the somatic and germline gene mutations in R/R T-ALL/LBL and evaluated the prognosis after transplantation. Based on our limited study, we found that using CD7 CAR T cells followed by allo-HSCT greatly enhanced the long-term DFS of chemo resistant T-ALL/LBL patients.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"31 2","pages":"Pages 73.e1-73.e11"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation and Cellular Therapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666636724007802","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

T-ALL is caused by abnormal proliferation of T cells. It comprises 25%-50% of ALL cases in children and adults. Outlook for R/R T-ALL/LBL and patients over 60 is even dimmer. The treatment is challenging due to its biological and genetic diversity, limiting the development of effective targeted and immunotherapeutic strategies. Salvaged allo-HSCT offers only 20% to 30% DFS. This current study retrospectively analyzed 90 patients with R/R T-ALL (40, 44.4%) or T-LBL (50, 55.6%) treated at Beijing Gobroad Boren Hospital from February 2018 to January 2023. The median age was 14 (range: 2–65) y old. Somatic and germline gene mutations were detected by sequencing pretransplant. Thirty-two (35.6%) patients were sensitive to chemotherapy and achieved CR before transplant (CR group), and 58 (64.4%) cases were resistant to chemotherapy and in non-remission (NR) pre-HSCT. Forty-one of 58 patients in NR received CD7 CAR-T before allo-HSCT (CART group) and the rest 17 patients in NR underwent salvaged transplant (NR group). The results indicate that CD7 CAR-T group have OS (p = .029; 2-y OS rates: 54.4% [95% CI: 38.9% to 76%]) and DFS (p = .00032; 2-y DFS: 51.0% (95% CI: 36.9% to 70.7%)) similar to those in the CR group, but better than those in the NR group. The CIR for CD7 CAR-T group and CR group was significantly lower than NR group after 1 y (p = .0016; CAR-T group 2-y CIR: 31.67% (95% CI: 19.3% to 49.2%)). Our study examined the somatic and germline gene mutations in R/R T-ALL/LBL and evaluated the prognosis after transplantation. Based on our limited study, we found that using CD7 CAR T cells followed by allo-HSCT greatly enhanced the long-term DFS of chemo resistant T-ALL/LBL patients.

查看原文本刊更多论文

CD7 CART疗法与异基因造血干细胞移植衔接可显著改善难治/复发T-ALL/LBL的长期生存率。

T-ALL 由 T 细胞异常增殖引起。它占儿童和成人 ALL 病例的 25%-50%。R/R T-ALL/LBL 和 60 岁以上患者的前景更加暗淡。由于其生物学和遗传学的多样性，限制了有效的靶向和免疫治疗策略的发展，因此治疗具有挑战性。挽救性异体造血干细胞移植的 DFS 仅为 20%-30%。本研究回顾性分析了2018年2月至2023年1月在北京国博博仁医院接受治疗的90例R/R T-ALL（40例，44.4%）或T-LBL（50例，55.6%）患者。中位年龄为14岁（2-65岁）。移植前通过测序检测到体细胞和种系基因突变。32例（35.6%）患者对化疗敏感并在移植前达到CR（CR组），58例（64.4%）对化疗耐药并在HSCT前处于非缓解期（NR）。58例NR患者中有41例在allo-HSCT前接受了CD7 CAR-T治疗（CART组），其余17例NR患者接受了挽救性移植（NR组）。结果表明，CD7 CAR-T 组的 OS（P=0.029；2 年 OS 率：54.4% (95% C.)；2 年 OS 率：54.4% (95% C.))54.4%（95% CI：38.9-76.0%））和 DFS（p=0.00032；2 年 DFS：51.0%（95% CI：36.9-70.7%））与 CR 组相似，但优于 NR 组。一年后，CD7 CAR-T 组和 CR 组的 CIR 明显低于 NR 组（P=0.0016；CAR-T 组 2 年 CIR：31.67%（95% CI：19.3-49.2%））。我们的研究考察了R/R T-ALL/LBL的体细胞和种系基因突变，并评估了移植后的预后。在有限的研究基础上，我们发现使用 CD7 CAR T 细胞后进行异体 HSCT 大大提高了化疗耐药 T-ALL/LBL 患者的长期 DFS。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊