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:Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Mantle Cell Lymphoma: Real-World Outcomes, Late Relapse Patterns, and Clinical Utility in the Chimeric Antigen Receptor T-Cell Era.
Allogeneic Hematopoietic Cell Transplantation for Relapsed or Refractory Mantle Cell Lymphoma: Real-World Outcomes, Late Relapse Patterns, and Clinical Utility in the Chimeric Antigen Receptor T-Cell Era.
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在这个真实世界队列中,异基因造血干细胞移植为一部分复发/难治性套细胞淋巴瘤患者提供了持续的疾病控制,包括适合挽救治疗的晚期局限性复发。
异基因造血细胞移植(alloHCT)仍是复发/难治性(r/r)套细胞淋巴瘤(MCL)的潜在治愈性选择,但在布鲁顿酪氨酸激酶抑制剂(BTKi)和CAR-T 细胞疗法时代,其作用已发生变化。关于长期结局及复发后挽救策略的真实世界证据有限。
回顾性分析2001至2017年间接受alloHCT的29例r/r MCL患者,预处理采用较高强度或减低强度方案。评估总生存期(OS)、无进展生存期(PFS)、复发发生率和非复发死亡率(NRM),重点关注复发时间及其处理,并探索性比较不同预处理方案。
中位随访143个月(95% CI:104个月至未达到)时,3年OS和PFS分别为41%和34%。38%的患者复发,其中超过四分之一为移植后较晚(>12个月)发生且主要局限于局部的复发。单独挽救性放疗或联合BTKi治疗,使约三分之二患者获得持久疾病控制。较高强度与减低强度预处理之间存在差异,但分析仅具探索性,且未得出统计学确证结论。
在这一真实世界队列中,alloHCT使部分r/r MCL患者获得持续疾病控制,包括可通过挽救治疗处理的晚期局限性复发。当前alloHCT实施频率已降低,因此此类数据对于CAR-T 不适用或治疗失败后的决策至关重要,尤其是在CAR-T 可及性受限的地区。这些发现支持alloHCT在现代治疗格局中继续发挥选择性作用,并强调在CAR-T 时代需要真实世界证据指导患者选择和治疗排序。 试验注册:作者确认本研究无需进行临床试验注册。
Allogeneic hematopoietic cell transplantation (alloHCT) remains a curative option for relapsed or refractory (r/r) mantle cell lymphoma (MCL), although its role has shifted in the era of Bruton tyrosine kinase inhibition (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy. Real-world evidence on long-term outcomes and salvage strategies after relapse is limited.
We performed a retrospective analysis of 29 patients with r/r MCL who underwent alloHCT between 2001 and 2017 using either higher-intensity or reduced-intensity conditioning. Outcomes assessed included overall survival (OS), progression-free survival (PFS), relapse incidence, and non-relapse mortality (NRM), focusing on relapse timing and management. Conditioning regimens were compared exploratorily.
With a median follow-up of 143 months (95% CI: 104-NR), 3-year OS and PFS were 41% and 34%, respectively. Relapse occurred in 38% of patients, including over one quarter with late (> 12-month), predominantly localized relapse. Salvage radiotherapy, alone or combined with BTKi, achieved durable disease control in about two-thirds of patients. Differences between higher-intensity and reduced-intensity conditioning were observed but remained exploratory and not statistically conclusive.
In this real-world cohort, alloHCT provided sustained disease control for a subset of r/r MCL patients, including late, localized relapse amenable to salvage therapy. As alloHCT is now performed less frequently, such datasets are critical for decision-making in patients after CAR-T ineligibility or failure, especially where CAR-T access is limited. These findings support a continued, selective role for alloHCT in the modern treatment landscape and emphasize the need for real-world evidence to guide patient selection and sequencing in the CAR-T era. TRIAL REGISTRATION: The authors have confirmed clinical trial registration is not needed for this submission.
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