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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Total Body Irradiation Versus Chemotherapy-Only Conditioning in Autologous Haematopoietic Stem Cell Transplantation for Relapsed/Refractory Large B-cell Lymphoma.
Total Body Irradiation Versus Chemotherapy-Only Conditioning in Autologous Haematopoietic Stem Cell Transplantation for Relapsed/Refractory Large B-cell Lymphoma.
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尽管接受 TBI 的患者存在更多不良特征,但仅化疗与基于 TBI 的清淋预处理患者之间的 PFS 或 OS 无差异。
在CAR-T 细胞疗法时代,对于无法获得CAR-T 治疗或晚期化疗敏感复发(>12个月)的大B细胞淋巴瘤(LBCL)患者,自体干细胞移植(ASCT)仍有作用。通常ASCT预处理方案仅采用化疗。鉴于LBCL对放疗敏感,本研究回顾性评估与单纯化疗预处理相比,全身照射(TBI)预处理能否改善ASCT结局。
研究纳入2012至2021年在本中心接受ASCT的复发/难治性(r/r)LBCL患者。由于TBI通常仅用于较年轻患者,研究者排除了单纯化疗组中年龄超过TBI组最高年龄的患者,最终数据集包括56例(TBI组19例;化疗组37例)。
TBI组具有更多不良特征,包括男性比例较高(89.5%比62.2%)、复发发生于12个月后者较多(52.6%比32.4%),以及从诊断到ASCT的时间较短(中位数11.7比21.8个月)。TBI组和化疗组2年无进展生存期(PFS)分别为58%(95%置信区间39%–85%)和67%(53%–84%);2年总生存期(OS)分别为79%(63%–100%)和80%(68%–95%)。多变量分析中,TBI相较化疗导致PFS失败的风险比为1.35(95%置信区间0.59–3.12),死亡风险比为1.33(95%置信区间0.49–3.58)。预处理方案与PFS无关,而ASCT时正电子发射断层扫描(PET)阳性与PFS失败相关(风险比6.97,95%置信区间2.98–16.27,P<0.001)。
尽管接受TBI的患者具有更多不良特征,单纯化疗和TBI预处理患者的PFS或OS并无差异。尽管该研究仅用于提出假设,结果提示TBI可能部分抵消不良特征的影响。
We included patients with relapsed/refractory (r/r) LBCL who underwent ASCT at our centre (2012-2021). As TBI is generally offered only to younger patients, we excluded patients in the chemo-only group who were older than the oldest patient in the TBI group, leaving 56 patients in the final dataset (TBI: 19; chemo: 37).
The TBI cohort had more adverse features including male sex (89.5% vs 62.2%), relapse 12 months (52.6% vs 32.4%), and shorter time between diagnosis and ASCT (median: 11.7 vs 21.8 months). Two-year progression-free survival (PFS) was 58% (95% confidence interval [CI]: 39%-85%) and 67% (53%-84%) in TBI and chemotherapy cohorts, respectively. Two-year overall survival (OS) was 79% (63%-100%) and 80% (68%-95%) in TBI and chemotherapy cohorts, respectively. Multivariable hazard ratio (HR) of PFS failure (TBI vs chemo) was 1.35 (95% CI: 0.59-3.12). The HR of death was 1.33 (95% CI: 0.49-3.58). While conditioning regimen was not associated with PFS, positron emission tomography (PET) positivity at time of ASCT (HR: 6.97, 95% CI: 2.98-16.27, P < 0.001) was associated with PFS failure.
Despite the presence of more adverse features among patients treated with TBI, there was no difference in PFS or OS among patients that underwent chemo-only vs TBI-based conditioning. Though hypothesis generating, this suggests that TBI may be able to partially compensate for adverse fatures.
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