决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Indications for Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation in Adults: State of the Art.
Indications for Autologous and Allogeneic Hematopoietic Stem-Cell Transplantation in Adults: State of the Art.
造血干细胞移植(HSCT)已从一种针对原本致命性白血病的挽救性治疗手段,发展为一种可治愈几乎所有血液系统恶性肿瘤及多种非恶性疾病的治疗方式。
造血干细胞移植(HSCT)已从一种针对原本致命的白血病的挽救性手段,演变为涵盖几乎所有血液系统恶性肿瘤及若干非恶性疾病的治愈性治疗方式。当代格局被三股汇聚的力量所重塑:疾病特异性风险分层的精细化(急性髓系白血病的 European LeukemiaNet [ELN] 2022、骨髓增生异常综合征的 Molecular International Prognostic Scoring System [IPSS-M]、骨髓纤维化的 Mutation-Enhanced International Prognostic Scoring System [MIPSS70+ v2.0] 及 Myelofibrosis Transplant Scoring System [MTSS]);将可测量残留病(MRD)整合进动态的、基于反应调整的移植决策;以及免疫效应细胞疗法的获批,这些疗法已将移植从若干长期存在的适应证中取代,同时创造了新的适应证(移植桥接、CAR-T 后巩固)。与此同时,移植后环磷酰胺(PTCy)已在很大程度上使全相合同胞、全相合无关及不合替代供者之间的结局趋于均等,而新型药物(ruxolitinib、belumosudil、axatilimab)已实质性降低了移植物抗宿主病(GVHD)的发病率。本叙述性综述综合了成人自体(auto-HSCT)和异基因(allo-HSCT)移植的当前适应证,并指出了随机数据仍在成熟中的持续争议领域。在所有适应证中,临床医生的问题正从“是否移植?”转向“哪个供者、哪种预处理、哪种桥接以及哪种移植后维持?”,每一项均根据疾病生物学、MRD 轨迹和患者体能状态进行个体化调整。
Hematopoietic stem-cell transplantation (HSCT) has evolved from a salvage procedure for otherwise-fatal leukemia into a curative modality spanning nearly every hematological malignancy and several non-malignant disorders. The contemporary landscape has been reshaped by three converging forces: the refinement of disease-specific risk stratification (European LeukemiaNet [ELN] 2022 for acute myeloid leukemia, Molecular International Prognostic Scoring System [IPSS-M] for myelodysplastic syndromes, Mutation-Enhanced International Prognostic Scoring System [MIPSS70+ v2.0], and Myelofibrosis Transplant Scoring System [MTSS] for myelofibrosis); the integration of measurable residual disease (MRD) into dynamic, response-adapted transplant decisions; and the approval of immune effector cell therapies that have displaced transplantation from several long-standing indications while creating new ones (bridge-to-transplant, post-CAR-T consolidation). In parallel, post-transplant cyclophosphamide (PTCy) has largely equalized outcomes across matched sibling, matched unrelated, and mismatched alternative donors, and novel agents (ruxolitinib, belumosudil, axatilimab) have materially reduced graft-versus-host disease (GVHD) morbidity. This narrative review synthesizes current indications for autologous (auto-HSCT) and allogeneic (allo-HSCT) transplantations in adults, and flags areas of persistent controversy where randomized data are still maturing. Across all indications, the clinician's question is shifting from "transplant or not?" towards "which donor, which conditioning, which bridge, and which post-transplant maintenance?", each tailored to disease biology, MRD trajectory, and patient fitness.
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