CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Baseline circulating tumour DNA and total metabolic tumour volume as early outcome predictors in aggressive large B-cell lymphoma. A real-world 112-patient cohort.
Baseline circulating tumour DNA and total metabolic tumour volume as early outcome predictors in aggressive large B-cell lymphoma. A real-world 112-patient cohort.
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约20%至50%的大B细胞淋巴瘤(LBCL)患者结局不佳。本研究评估循环肿瘤DNA(ctDNA)与总代谢肿瘤体积(TMTV)联合的预后价值。单中心观察研究纳入112例新诊断LBCL患者,均接受R-CHOP或类似化疗。以靶向40基因淋巴瘤panel的无细胞DNA测序计算ctDNA负荷,并通过全自动AI病灶分割测量TMTV。95例血浆检出ctDNA,中位浓度为3.15 log hGE/mL;102例有TMTV数据,中位501 mL。ctDNA高负荷(>3.57 log hGE/mL)或TMTV高(>200 mL)均与较短1年PFS相关,分别为44%比83%(p<0.001)及64%比97%(p=0.002)。联合两指标可划分三类预后组,ctDNA和TMTV均高者PFS最短(p<0.001)。尽管随访较短,二者联合改善了侵袭性LBCL患者风险分层。未来极高危患者可能适合一线CAR-T 或双特异性抗体。
Approximately 20%-50% of patients with large B-cell lymphoma (LBCL) experience poor outcomes.
We aimed to evaluate the combined prognostic value of circulating tumour DNA (ctDNA) and total metabolic tumour volume (TMTV) in LBCL. This observational single-centre study included 112 newly diagnosed LBCL patients, receiving R-CHOP/R-CHOP-like chemotherapies. CtDNA load was calculated following next-generation sequencing of cell-free DNA (cfDNA) using a targeted 40-gene lymphopanel. TMTV was measured using a fully automated artificial intelligence-based method for lymphoma lesion segmentation. CtDNA was detected in cfDNA samples from 95 patients with a median concentration of 3. 15 log haploid genome equivalents per mL.
TMTV measurements were available for 102 patients. The median TMTV was 501 mL. High ctDNA load (>3. 57 log hGE/mL) or high TMTV (>200 mL) were associated with shorter 1-year PFS (44% vs. 83%, p < 0. 001 and 64% vs. 97%, p = 0. 002, respectively). When combined, three prognostic groups were identified.
The shortest PFS was observed when both TMTV and ctDNA load were high (p < 0. 001). Even with a short follow up, combining ctDNA load with TMTV improved the risk stratification of patients with aggressive LBCL. In the near future, very high-risk patients could benefit from CAR T-cell therapy or bispecific antibodies as first-line treatments.
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