决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL.
CD7 CART Therapy Bridging Allo-HSCT Remarkably Improves Long-Term DFS in Refractory/Relapsed T-ALL/LBL.
它占儿童和成人急性淋巴细胞白血病(ALL)病例的 25%-50%。
T细胞急性淋巴细胞白血病(T-ALL)由T细胞异常增殖引起,占儿童和成人ALL病例的25%–50%。复发/难治性T-ALL/T细胞淋巴母细胞淋巴瘤(T-LBL)患者及60岁以上患者的预后更差。由于其生物学和遗传学异质性,开发有效靶向及免疫治疗策略面临困难。挽救性异基因造血干细胞移植(allo-HSCT)的无病生存率(DFS)仅为20%–30%。本研究回顾性分析2018年2月至2023年1月北京高博博仁医院治疗的90例复发/难治性患者,包括40例T-ALL(44.4%)和50例T-LBL(55.6%)。患者中位年龄为14岁(范围2–65岁)。研究通过测序检测移植前的体细胞和生殖系基因突变。32例(35.6%)患者对化疗敏感,移植前达到完全缓解(CR组);58例(64.4%)患者对化疗耐药,移植前未缓解(NR组)。NR患者中,41例在allo-HSCT前接受CD7 CAR-T治疗(CART组),其余17例接受挽救性移植(NR组)。结果显示,CART组的总生存期(OS;p=0.029;2年OS率54.4%,95% CI:38.9%–76%)和DFS(p=0.00032;2年DFS率51.0%,95% CI:36.9%–70.7%)与CR组相近,但优于NR组。1年后,CART组和CR组的累积复发发生率(CIR)显著低于NR组(p=0.0016;CART组2年CIR为31.67%,95% CI:19.3%–49.2%)。本研究分析了复发/难治性T-ALL/T-LBL患者的体细胞和生殖系基因突变,并评估了移植后的预后。基于本项有限研究,研究者发现,先给予CD7 CAR-T细胞再进行allo-HSCT,可显著提高化疗耐药T-ALL/T-LBL患者的长期DFS。
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.
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