不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel:ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytokine-Induced Killer Cell Therapy as a Postremission Strategy in High-Risk Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Prospective Investigator-Initiated Clinical Study.
Cytokine-Induced Killer Cell Therapy as a Postremission Strategy in High-Risk Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Prospective Investigator-Initiated Clinical Study.
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在高危非霍奇金淋巴瘤(NHL)达到完全缓解(CR)的患者中,强化化疗和自体干细胞移植(ASCT)可提供额外获益。然而,尽管有这些获益,微小残留病导致的复发以及高危的延迟免疫重建相关非典型感染仍导致移植后早期发病率和死亡率升高。这凸显了需要创新策略来优化治疗应用并改善结局。
因此,我们旨在通过研究细胞因子诱导的杀伤(CIK)细胞的潜力,寻找一种创新策略来优化治疗应用并改善其结局。我们假设我们的方法将通过靶向残留病灶和支持免疫恢复来改善高危侵袭性NHL移植后的结局,从而延长无进展生存期(PFS)并降低机会性感染风险。在这项单中心研究中,我们前瞻性评估了20例在接受初始或挽救治疗后达到完全缓解的高危NHL患者中,ASCT后早期输注CIK细胞的给药情况。主要终点和次要终点分别为2年PFS和免疫重建相关安全性特征评估。来自CD3+细胞比例较高(中位数,97.5%)的参与者的CIK细胞,包括CD3+CD56+自然杀伤样T细胞(中位数,28.6%),通过NKG2D受体过表达(中位数,73.6%)和体外裂解K562细胞系表现出强效的细胞毒性作用。
ASCT后,CIK细胞(2.65 × 10 7至3.78 × 10 9/kg)在中位14(10至18)天时输注;仅2例患者出现轻度发热;79.8%(95%置信区间,49.4%至93.1%)达到中位2年PFS(22.6[2.3至37.9] 个月),且无未控制的巨细胞病毒(CMV)DNA血症或感染,CIK 细胞产品中 CMV-pp65 特异性干扰素-γ 反应完整。CIK 细胞与移植后早期免疫重建期间 T 细胞亚群功能活性的改善相关。ASCT 后 CIK 细胞输注作为高危 NHL 的缓解后治疗,可能预防复发和机会性感染。
In high-risk non-Hodgkin lymphoma (NHL) with complete remission (CR), intensive chemotherapy and autologous stem cell transplantation (ASCT) provide additional benefits.
However, despite the benefits, minimal residual disease-induced relapse and high-risk delayed immune-reconstitution-based-atypical infections contribute to early post-transplant morbidity and mortality. This highlights the need for innovative strategies to refine treatment application and improve outcomes.
Thus, we aimed to find an innovative strategy to refine therapeutic applications and improve their outcomes by examining the potential of cytokine-induced killer (CIK) cells.
We hypothesized that our method would improve post-transplant outcomes in high-grade aggressive NHL by targeting residual disease and supporting immune recovery, thereby enhancing progression-free survival (PFS) and reducing opportunistic infection risk. In this single-center study, we prospectively evaluated early post-ASCT CIK cell-infusion administration in 20 high-risk patients with NHL who achieved complete remission, after upfront or salvage treatment. The primary and secondary endpoints were 2-year PFS and immune reconstitution-associated safety profile evaluation, respectively. CIK cells from participants with a high proportion of CD3+ cells (median, 97. 5%), including CD3+CD56+ natural killer-like T cells (median, 28.
6%), demonstrated potent cytotoxic effects through NKG2D-receptor overexpression (median, 73. 6%) and in vitro lysis of K562 cell line. Post-ASCT, CIK cells (2. 65 × 10 7 to 3. 78 × 10 9 /kg) were infused at a median 14 (10 to 18)-day duration; only two patients were mildly febrile; 79. 8% (95% confidence interval, 49. 4% to 93. 1%) achieved median 2-yr PFS (22. 6 [2. 3 to 37.
9] mo), without uncontrolled cytomegalovirus (CMV) DNAemia or infections with intact CMV-pp65-specific interferon-γ response in CIK-cell product. CIK cells were associated with improved functional activity of T-cell subsets during early post-transplant immune reconstitution. Post-ASCT CIK cell infusion as post-remission therapy for high-risk NHL may prevent relapse and opportunistic infections.
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