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:Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia.
Role of chimeric antigen receptor T-cell therapy: bridge to transplantation or stand-alone therapy in pediatric acute lymphoblastic leukemia.
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综述目的:讨论CAR-T 细胞治疗,无论是否联合巩固性造血干细胞移植(HCT),对B系急性淋巴细胞白血病(B-ALL)儿童及年轻成人的治愈潜力。近期发现:靶向CD19的CAR-T 可使复发/难治性B-ALL患者获得持久缓解并延长生存。CD19 CAR-T 诱导缓解后,是否需要HCT巩固以治愈复发/难治性B-ALL仍有争议。初步证据提示,对未曾接受HCT的儿童,CAR-T 后巩固性HCT可改善无白血病生存。
然而,避免HCT相关远期不良影响是理想目标,因此需要识别复发高危患者,以便在必要时为其安排HCT,同时避免其他患者接受HCT。CAR-T 输注前疾病负荷较高、B细胞再生、以及CAR-T 治疗后通过流式细胞术或二代测序检出可测量残留病灶,均与较高复发风险相关,可能有助于识别需要巩固性HCT以预防复发的患者。总结:迫切需要确定何时单独使用CD19 CAR-T 可能治愈患者、何时需要巩固性HCT。本文讨论当前认识和未来方向。
PURPOSE OF REVIEW: To discuss the curative potential for chimeric antigen receptor T-cell (CAR-T) therapy, with or without consolidative hematopoietic stem cell transplantation (HCT) in the treatment of children and young adults with B lineage acute lymphoblastic leukemia (B-ALL).
RECENT FINDINGS: CAR-T targeting CD19 can induce durable remissions and prolong life in patients with relapsed/refractory B-ALL. Whether HCT is needed to consolidate remission and cure relapse/refractory B-ALL following a CD19 CAR-T induced remission remains controversial. Preliminary evidence suggests that consolidative HCT following CAR-T in HCT-na ve children improves leukemia-free survival.
However, avoiding HCT-related late effects is a desirable goal, so identification of patients at high risk of relapse is needed to appropriately direct those patients to HCT when necessary, while avoiding HCT in others.
High disease burden prior to CAR-T infusion, loss of B-cell aplasia and detection of measurable residual disease by flow cytometry or next-generation sequencing following CAR-T therapy associate with a higher relapse risk and may identify patients requiring consolidative HCT for relapse prevention. SUMMARY: There is a pressing need to determine when CD19 CAR-T alone is likely to be curative and when a consolidative HCT will be required.
We discuss the current state of knowledge and future directions.
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